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1.	Engström, Gunnar, et al. (författare) Pulmonary function and atherosclerosis in the general population : causal associations and clinical implications 2024 Ingår i: European Journal of Epidemiology. - : Springer Nature. - 0393-2990 .- 1573-7284. ; 39:1, s. 35-49 Tidskriftsartikel (refereegranskat)abstract Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50–64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.
2.	Abdellah, Tebani, et al. (författare) Integration of molecular profiles in a longitudinal wellness profiling cohort. 2020 Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1 Tidskriftsartikel (refereegranskat)abstract An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies andimmune cell profiling, complementedwith gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.
3.	Ahlberg, Anders, et al. (författare) Studenters självkänsla, självständighet och kreativa delaktighet - hur kan detta befrämjas i kurser och program? 2009 Ingår i: Proceedings Utvecklingskonferens Lunds universitet 2009. - 9789197797429 ; , s. 31-31 Konferensbidrag (refereegranskat)
4.	Alsaqal, Salem, et al. (författare) The Combination of MR Elastography and Proton Density Fat Fraction Improves Diagnosis of Nonalcoholic Steatohepatitis. 2022 Ingår i: Journal of Magnetic Resonance Imaging. - : John Wiley & Sons. - 1053-1807 .- 1522-2586. ; 56:2, s. -379 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is rapidly increasing worldwide. It is subdivided into nonalcoholic fatty liver (NAFL) and the more aggressive form, nonalcoholic steatohepatitis (NASH), which carries a higher risk of developing fibrosis and cirrhosis. There is currently no reliable non-invasive method for differentiating NASH from NAFL.PURPOSE: To investigate the ability of magnetic resonance imaging (MRI)-based imaging biomarkers to diagnose NASH and moderate fibrosis as well as assess their repeatability.STUDY TYPE: Prospective.SUBJECTS: Sixty-eight participants (41% women) with biopsy-proven NAFLD (53 NASH and 15 NAFL). Thirty participants underwent a second MRI in order to assess repeatability.FIELD STRENGTH/SEQUENCE: 3.0 T; MR elastography (MRE) (a spin-echo echo-planar imaging [SE-EPI] sequence with motion-encoding gradients), MR proton density fat fraction (PDFF) and R2* mapping (a multi-echo three-dimensional gradient-echo sequence), T1 mapping (a single-point saturation-recovery technique), and diffusion-weighted imaging (SE-EPI sequence).ASSESSMENT: Quantitative MRI measurements were obtained and assessed alone and in combination with biochemical markers (cytokeratin-18 [CK18] M30, alanine transaminase [ALT], and aspartate transaminase [AST]) using logistic regression models. Models that could differentiate between NASH and NAFL and between moderate to advanced fibrosis (F2-4) and no or mild fibrosis (F0-1), based on the histopathological results, were identified.STATISTICAL TESTS: Independent samples t-test, Pearson's chi-squared test, area under the receiver operating characteristic curve (AUROC), Spearman's correlation, intra-individual coefficient of variation, and intraclass correlation coefficient (ICC). Statistical significance was set at P < 0.05.RESULTS: There was a significant difference between the NASH and NAFL groups with liver stiffness assessed with MRE, CK18 M30, and ALT, with an AUROC of 0.74, 0.76, and 0.70, respectively. Both MRE and PDFF contributed significantly to a bivariate model for diagnosing NASH (AUROC = 0.84). MRE could significantly differentiate between F2-4 and F0-1 (AUROC = 0.74). A model combining MRE with AST improved the diagnosis of F2-4 (AUROC = 0.83). The ICC for repeatability was 0.94 and 0.99 for MRE and PDFF, respectively.DATA CONCLUSION: MRE can potentially diagnose NASH and differentiate between fibrosis stages. Combining MRE with PDFF improves the diagnosis of NASH.LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.
5.	Gummesson, Anders, 1973, et al. (författare) Longitudinal plasma protein profiling of newly diagnosed type 2 diabetes 2021 Ingår i: EBioMedicine. - : Elsevier B.V.. - 2352-3964. ; 63 Tidskriftsartikel (refereegranskat)abstract Background: Comprehensive proteomics profiling may offer new insights into the dysregulated metabolic milieu of type 2 diabetes, and in the future, serve as a useful tool for personalized medicine. This calls for a better understanding of circulating protein patterns at the early stage of type 2 diabetes as well as the dynamics of protein patterns during changes in metabolic status. Methods: To elucidate the systemic alterations in early-stage diabetes and to investigate the effects on the proteome during metabolic improvement, we measured 974 circulating proteins in 52 newly diagnosed, treatment-naïve type 2 diabetes subjects at baseline and after 1 and 3 months of guideline-based diabetes treatment, while comparing their protein profiles to that of 94 subjects without diabetes. Findings: Early stage type 2 diabetes was associated with distinct protein patterns, reflecting key metabolic syndrome features including insulin resistance, adiposity, hyperglycemia and liver steatosis. The protein profiles at baseline were attenuated during guideline-based diabetes treatment and several plasma proteins associated with metformin medication independently of metabolic variables, such as circulating EPCAM. Interpretation: The results advance our knowledge about the biochemical manifestations of type 2 diabetes and suggest that comprehensive protein profiling may serve as a useful tool for metabolic phenotyping and for elucidating the biological effects of diabetes treatments. Funding: This work was supported by the Swedish Heart and Lung Foundation, the Swedish Research Council, the Erling Persson Foundation, the Knut and Alice Wallenberg Foundation, and the Swedish state under the agreement between the Swedish government and the county councils (ALF-agreement).
6.	Hockings, Paul, 1956, et al. (författare) BIVARIATE MR IMAGING BIOMARKER TO IMPROVE PREDICTION OF ADVANCED FIBROSIS IN SUBJECTS WITH BIOPSY PROVEN NAFLD 2020 Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract Abstract not available
7.	Olofsson, Louise, 1977, et al. (författare) Preliminary report: Zn-alpha2-glycoprotein genotype and serum levels are associated with serum lipids. 2010 Ingår i: Metabolism. - : Elsevier BV. - 1532-8600 .- 0026-0495. ; 59:9, s. 1316-1318 Tidskriftsartikel (refereegranskat)abstract Zn-alpha2-glycoprotein (ZAG) is a serum protein implicated in cancer cachexia and lipolysis. Our aim was to investigate serum levels of ZAG and polymorphisms in the ZAG gene in relation to serum lipids in man. Serum levels of ZAG correlated with serum levels of cholesterol (P = .00088) in healthy subjects and during weight loss (P = .059). The ZAG genotype was associated with total cholesterol (P = .014) and low-density lipoprotein cholesterol (P = .026) in healthy subjects, and the associations were replicated in an additional cohort (P = .0017 and P = .060, respectively). Our data indicate that ZAG plays a role in lipid metabolism.
8.	Sonesson, Anders, et al. (författare) Forskningsbaserad utveckling av undervisning och lärande inom medicinska professionsutbildningar 2014 Ingår i: Vetenskapliga perspektiv på lärande, undervisning och utbildning i olika institutionella sammanhang – utbildningsvetenskaplig forskning vid Lunds universitet. - 9789174738629 ; , s. 351-366 Bokkapitel (refereegranskat)
9.	Vessby, Johan, et al. (författare) Non-Invasive Imaging Biomarkers to Detect Nash in Subjects with NAFLD 2020 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
10.	Östgren, Carl Johan, et al. (författare) Prevalence of atherosclerosis in individuals with prediabetes and diabetes compared to normoglycaemic individuals-a Swedish population-based study. 2023 Ingår i: Cardiovascular diabetology. - : BioMed Central (BMC). - 1475-2840. ; 22:1 Tidskriftsartikel (refereegranskat)abstract Patients with type 2 diabetes have an increased risk of death and cardiovascular events and people with diabetes or prediabetes have been found to have increased atherosclerotic burden in the coronary and carotid arteries. This study will estimate the cross-sectional prevalence of atherosclerosis in the coronary and carotid arteries in individuals with prediabetes and diabetes, compared with normoglycaemic individuals in a large population-based cohort.The 30,154 study participants, 50-64years, were categorized according to their fasting glycaemic status or self-reported data as normoglycaemic, prediabetes, and previously undetected or known diabetes. Prevalence of affected coronary artery segments, severity of stenosis and coronary artery calcium score (CACS) were determined by coronary computed tomography angiography. Total atherosclerotic burden was assessed in the 11 clinically most relevant segments using the Segment Involvement Score and as the presence of any coronary atherosclerosis. The presence of atherosclerotic plaque in the carotid arteries was determined by ultrasound examination.Study participants with prediabetes (n=4804, 16.0%) or diabetes (n=2282, 7.6%) had greater coronary artery plaque burden, more coronary stenosis and higher CACS than normoglycaemic participants (all, p<0.01). Among male participants with diabetes 35.3% had CACS≥100 compared to 16.1% among normoglycaemic participants. For women, the corresponding figures were 8.9% vs 6.1%. The prevalence of atherosclerosis in the coronary arteries was higher in participants with previously undetected diabetes than prediabetes, but lower than in patients with known diabetes. The prevalence of any plaque in the carotid arteries was higher in participants with prediabetes or diabetes than in normoglycaemic participants.In this large population-based cohort of currently asymptomatic people, the atherosclerotic burden in the coronary and carotid arteries increased with increasing degree of dysglycaemia. The finding that the atherosclerotic burden in the coronary arteries in the undetected diabetes category was midway between the prediabetes category and patients with known diabetes may have implications for screening strategies and tailored prevention interventions for people with dysglycaemia in the future.
11.	Behre, Carl Johan, 1968, et al. (författare) Dissociation between adipose tissue expression and serum levels of adiponectin during and after diet-induced weight loss in obese subjects with and without the metabolic syndrome 2007 Ingår i: Metabolism: Clinical and Experimental. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 56:8, s. 1022-8 Tidskriftsartikel (refereegranskat)abstract The study aimed to examine if dysmetabolic subjects (MetS+) have lower adiponectin gene expression and lower circulating adiponectin levels than non-dysmetabolic obese subjects (MetS-) at baseline, if adiponectin expression and adiponectin concentration rise more in the dysmetabolic group during weight loss, and if v-SNARE Vti1a (vesicle transport soluble NSF attachment protein receptor vps10p tail interacting 1a) expression increases during the weight loss, as a mechanism for increased adiponectin secretion. Twenty-one obese MetS+ and 19 obese MetS- subjects underwent a very low-energy diet for 16 weeks followed by 2 weeks of refeeding. Abdominal subcutaneous adipose tissue biopsies and blood samples were taken before, during, and after dieting for DNA microarray, reverse transcriptase-polymerase chain reaction, and biochemical analyses. Serum adiponectin was also assessed in a sex- and age-matched healthy, nonobese reference group. Weight decreased by 26.3+/-9.8 kg in the MetS+ group and 28.2+/-8.4 kg in the MetS- group with concomitant reductions in insulin, hemoglobin A1c, and triglycerides that were more pronounced in the MetS+ group. Initially, the MetS+ subjects had lower serum adiponectin, but the differences disappeared at week 8, with a continuous increase in serum adiponectin throughout the study in both groups to a level that was higher than in the reference group. The expression of adiponectin and v-SNARE Vti1a did not differ between the groups or over time. In conclusion, obese subjects with the metabolic syndrome had lower circulating adiponectin than subjects without the syndrome. Weight loss increased serum levels of adiponectin without a parallel increase in adiponectin gene expression. The mechanisms involved in the regulation of adiponectin levels merits further investigation.
12.	Behre, Carl Johan, 1968, et al. (författare) Hypoxia-inducible factor 1 is correlated to serum adiponectin levels and measures of obesity and insulin sensitivity in vivo 2009 Ingår i: International Congress on Prediabetes and the Metabolic Syndrome. Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract Title: Hypoxia-inducible factor 1 is correlated to serum adiponectin levels and measures of obesity and insulin sensitivity in vivo Background: Hypoxia has been shown to decrease adiponectin in vitro. Adiponectin levels are negatively associated to type 2 diabetes and cardiovascular diseases. Recently, it was shown that Hypoxia-inducible factor 1α (HIF-1) regulates adiponectin expression in murine cardiomyocytes. The present study was performed to examine the association between HIF-1 expression and serum adiponectin levels, measures of adiposity and insulin resistance in humans. Methods: Abdominal subcutaneous adipose tissue biopsies were obtained from 24 subjects diagnosed with and without the metabolic syndrome. HIF-1 gene expression was assessed by individual DNA microarray analyses. Adipose tissue depots were assessed with computerized tomography. Anthropometrics were performed. Circulating levels of insulin, adiponectin, leptin, cholesterol, high-sensitivity C - reactive protein (hs-CRP) and fasting levels of insulin and glucose were measured by standard laboratory procedures. Results: In a univariate analysis, HIF-1 expression levels correlate to BMI (r=0.42, p=0.04), WHR (r=0.55, p=0.0058), total adipose tissue (r=0.46, p=0.022), subcutaneous adipose tissue ( r=0.49, p= 0.016),liver fat (r=0.44, p=0.030), fasting insulin (r=0.46, p=0.023), HOMA-index (r=0.46, p=0.023) and serum adiponectin (r= -0.42, p=0.0418). We observed no statistically significant correlations between HIF-1 gene expression and visceral adipose tissue, systolic blood pressure, serum cholesterol, hs-CRP or serum leptin. HIF-1 gene expression did not differ between the groups. Conclusions: We report that expression of HIF-1 is correlated to serum adiponectin, insulin sensitivity and measures of adiposity. There were no statistical differences in expression of HIF-1 between subjects with or without the metabolic syndrome. In this cross-sectional analysis, no conclusions can be drawn about causality.
13.	Bergström, Göran, et al. (författare) Self-report tool for identification of individuals with coronary atherosclerosis : the Swedish cardiopulmonary bioimage study 2024 Ingår i: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980. ; 13:14 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Coronary atherosclerosis detected by imaging is a marker of elevated cardiovascular risk. However, imaging involves large resources and exposure to radiation. The aim was, therefore, to test whether nonimaging data, specifically data that can be self-reported, could be used to identify individuals with moderate to severe coronary atherosclerosis.METHODS AND RESULTS: We used data from the population-based SCAPIS (Swedish CardioPulmonary BioImage Study) in individuals with coronary computed tomography angiography (n=25 182) and coronary artery calcification score (n=28 701), aged 50 to 64 years without previous ischemic heart disease. We developed a risk prediction tool using variables that could be assessed from home (self-report tool). For comparison, we also developed a tool using variables from laboratory tests, physical examinations, and self-report (clinical tool) and evaluated both models using receiver operating characteristic curve analysis, external validation, and benchmarked against factors in the pooled cohort equation. The self-report tool (n=14 variables) and the clinical tool (n=23 variables) showed high-to-excellent discriminative ability to identify a segment involvement score ≥4 (area under the curve 0.79 and 0.80, respectively) and significantly better than the pooled cohort equation (area under the curve 0.76, P<0.001). The tools showed a larger net benefit in clinical decision-making at relevant threshold probabilities. The self-report tool identified 65% of all individuals with a segment involvement score ≥4 in the top 30% of the highest-risk individuals. Tools developed for coronary artery calcification score ≥100 performed similarly.CONCLUSIONS: We have developed a self-report tool that effectively identifies individuals with moderate to severe coronary atherosclerosis. The self-report tool may serve as prescreening tool toward a cost-effective computed tomography-based screening program for high-risk individuals.
14.	Björnson, Elias, 1988, et al. (författare) Mediating role of atherogenic lipoproteins in the relationship between liver fat and coronary artery calcification 2023 Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1 Tidskriftsartikel (refereegranskat)abstract Non-alcoholic fatty liver disease (NAFLD) is associated with increased secretion of apoB-containing lipoproteins and increased risk of coronary heart disease (CHD). ApoB-containing lipoproteins include low-density lipoproteins (LDLs) and triglyceride-rich lipoproteins (TRLs); and since both LDLs and TRLs are causally related to CHD, they may mediate a portion of the increased risk of atherosclerosis seen in people with NAFLD. In a cohort of 4161 middle aged men and women, we performed mediation analysis in order to quantify the mediating effect of apoB-containing lipoproteins in the relationship between liver fat and atherosclerosis-as measured by coronary artery calcium score (CACS). We found plasma apoB to mediate 17.6% (95% CI 11-24) of the association between liver fat and CACS. Plasma triglycerides and TRL-cholesterol (both proximate measures of TRL particles) mediated 22.3% (95% CI 11-34) and 21.6% (95% CI 10-33) of the association respectively; whereas LDL-cholesterol mediated 5.4% (95% CI 2.0-9.4). In multivariable models, the mediating effect of TRL-cholesterol and plasma triglycerides showed, again, a higher degree of mediation than LDL-cholesterol, corroborating the results seen in the univariable models. In summary, we find around 20% of the association between liver fat and CACS to be mediated by apoB-containing lipoproteins. In addition, we find that TRLs mediate the majority of this effect whereas LDLs mediate a smaller effect. These results explain part of the observed CAD-risk burden for people with NAFLD and further suggest that TRL-lowering may be particularly beneficial to mitigate NAFLD-associated coronary artery disease risk.
15.	Björnson, Elias, 1988, et al. (författare) The relationship between genetic liver fat and coronary heart disease is explained by apoB-containing lipoproteins 2024 Ingår i: ATHEROSCLEROSIS. - 0021-9150 .- 1879-1484. ; 388 Tidskriftsartikel (refereegranskat)abstract Background: The relationship between genetically -driven liver fat and coronary heart disease (CHD) remains unclear. ApoB-containing lipoproteins are known causal factors for CHD and may explain this relationship. Methods and Results: We conducted a genome-wide association study (GWAS) in the UK Biobank to identify genetic variants associated with liver fat. We then investigated the effects that these genetic variants had on both apoB-containing lipoproteins and CHD. Using Mendelian Randomization (MR) analyses, we examined if the relationship between genetically -driven liver fat and CHD could be attributed to its effect on apoB-containing lipoproteins. We found 25 independent liver -fat associated single -nucleotide polymorphisms (SNPs) with differing effects on lipoprotein metabolism. The SNPs were classified into three groups/clusters. The first cluster (N = 3 SNPs) displayed lipoprotein -raising effects. The second cluster (N = 12 SNPs) displayed neutral effects on lipoproteins and the third cluster (N = 10 SNPs) displayed lipoprotein -lowering effects. For every 1% higher liver fat, the first cluster showed an increased risk of CHD (OR = 1.157 [95% CI: 1.108-1.208]). The second cluster showed a non -significant effect on CHD (OR = 0.988 [95% CI: 0.965-1.012], whereas the third cluster showed a protective effect of increased liver fat on CHD (OR = 0.942 [95% CI: 0.897-0.989]). When adjusting for apoB, the risk for CHD became null. Conclusions: Here, we identify 25 liver -fat associated SNPs. We find that SNPs that increase, decrease or have neutral effects on apoB-containing lipoproteins show increased, decreased or neutral effects on CHD, respectively. Therefore, the relationship between genetically -driven liver fat and CHD is mediated by the causal effect of apoB.
16.	Carlsson, Björn, 1958, et al. (författare) Differences in associations between HSD11B1 gene expression and metabolic parameters in subjects with and without impaired glucose homeostasis 2010 Ingår i: Diabetes Research and Clinical Practice. - : Elsevier BV. - 1872-8227 .- 0168-8227. ; 88:3, s. 252-258 Tidskriftsartikel (refereegranskat)abstract Aims: Animal studies indicate a role for 11 beta-hydroxysteroid dehydrogenase type 1 (HSD11B1) in the development of obesity. The association to glucose homeostasis is less clear. We investigated the relationship between HSD11B1 mRNA levels in adipose tissue and in skeletal muscle and anthropometric and metabolic measurements in humans with and without impaired glucose homeostasis. Methods: Twelve obese subjects with impaired glucose homeostasis (MetS+) and 12 obese controls (MetS-) received a Very Low Calorie Diet for 16 weeks and adipose tissue biopsies, blood samples and measurements were obtained. In a second cohort, skeletal muscle biopsies, blood samples and measurements were obtained from 18 subjects with type 2 diabetes (T2DM) and 17 subjects with normal glucose tolerance (NGT). Gene expression was measured by DNA microarray in both studies. Results: HSD11B1 mRNA levels were reduced during diet, and anthropometric measurements and metabolic parameters were associated with HSD11B1 mRNA levels in the MetS-group. However, in the MetS+ group these associations were lost or in opposite direction. This difference was also observed in skeletal muscle between T2DM and NGT. Conclusions: HSD11B1 mRNA levels are associated with metabolic parameters and anthropometric measurements in subjects with normal glucose homeostasis but not in subjects with impaired glucose homeostasis. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
17.	Dobritzsch, Doreen, 1972-, et al. (författare) beta-Ureidopropionase deficiency due to novel and rare UPB1 mutations affecting pre-mRNA splicing and protein structural integrity and catalytic activity 2022 Ingår i: Molecular Genetics and Metabolism. - : Elsevier. - 1096-7192 .- 1096-7206. ; 136:3, s. 177-185 Tidskriftsartikel (refereegranskat)abstract beta-Ureidopropionase is the third enzyme of the pyrimidine degradation pathway and catalyses the conversion of N-carbamyl-beta-alanine and N-carbamyl-beta-aminoisobutyric acid to beta-alanine and beta-aminoisobutyric acid, ammonia and CO2. To date, only a limited number of genetically confirmed patients with a complete beta-ureidopropionase deficiency have been reported. Here, we report on the clinical, biochemical and molecular findings of 10 newly identified beta-ureidopropionase deficient individuals. Patients presented mainly with neurological abnormalities and markedly elevated levels of N-carbamyl-beta-alanine and N-carbamyl-beta-aminoisobutyric acid in urine. Analysis of UPB1, encoding beta-ureidopropionase, showed 5 novel missense variants and two novel splice-site variants. Functional expression of the UPB1 variants in mammalian cells showed that recombinant beta-ureidopropionase carrying the p.Ala120Ser, p.Thr129Met, p.Ser300Leu and p.Asn345Ile variant yielded no or significantly decreased beta-ureidopropionase activity. Analysis of the crystal structure of human beta-ureidopropionase indicated that the point mutations affect substrate binding or prevent the proper subunit association to larger oligomers and thus a fully functional beta-ureidopropionase. A minigene approach showed that the intronic variants c.[364 + 6 T > G] and c.[916 + 1_916 + 2dup] led to skipping of exon 3 and 8, respectively, in the process of UPB1 pre-mRNA splicing. The c.[899C > T] (p.Ser300Leu) variant was identified in two unrelated Swedish beta-ureidopropionase patients, indicating that beta-ureidopropionase deficiency may be more common than anticipated.
18.	Dodig-Crnkovic, Tea, et al. (författare) Facets of individual-specific health signatures determined from longitudinal plasma proteome profiling 2020 Ingår i: Ebiomedicine. - : Elsevier BV. - 2352-3964. ; 57 Tidskriftsartikel (refereegranskat)abstract Background: Precision medicine approaches aim to tackle diseases on an individual level through molecular profiling. Despite the growing knowledge about diseases and the reported diversity of molecular phenotypes, the descriptions of human health on an individual level have been far less elaborate. Methods: To provide insights into the longitudinal protein signatures of well-being, we profiled blood plasma collected over one year from 101 clinically healthy individuals using multiplexed antibody assays. After applying an antibody validation scheme, we utilized > 700 protein profiles for in-depth analyses of the individuals' short-term health trajectories. Findings: We found signatures of circulating proteomes to be highly individual-specific. Considering technical and longitudinal variability, we observed that 49% of the protein profiles were stable over one year. We also identified eight networks of proteins in which 11-242 proteins covaried over time. For each participant, there were unique protein profiles of which some could be explained by associations to genetic variants. Interpretation: This observational and non-interventional study identifyed noticeable diversity among clinically healthy subjects, and facets of individual-specific signatures emerged by monitoring the variability of the circulating proteomes over time. To enable more personal hence precise assessments of health states, longitudinal profiling of circulating proteomes can provide a valuable component for precision medicine approaches.
19.	Ekblom Bak, Elin, 1981-, et al. (författare) Accelerometer derived physical activity patterns in 27.890 middle‐aged adults : The SCAPIS cohort study 2022 Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : John Wiley & Sons. - 0905-7188 .- 1600-0838. ; 32:5, s. 866-880 Tidskriftsartikel (refereegranskat)abstract The present study aims to describe accelerometer-assessed physical activity (PA) patterns and fulfillment of PA recommendations in a large sample of middle-aged men and women, and to study differences between subgroups of socio-demographic, socio-economic, and lifestyle-related variables. A total of 27 890 (92.5% of total participants, 52% women, aged 50–64 years) middle-aged men and women with at least four days of valid hip-worn accelerometer data (Actigraph GT3X+, wGT3X+ and wGT3X-BT) from the Swedish CArdioPulmonary bioImage Study, SCAPIS, were included. In total, 54.5% of daily wear time was spent sedentary, 39.1% in low, 5.4% in moderate, and only 0.1% in vigorous PA. Male sex, higher education, low financial strain, born in Sweden, and sedentary/light working situation were related to higher sedentary time, but also higher levels of vigorous PA. High BMI and having multiple chronic diseases associated strongly with higher sedentary time and less time in all three PA intensities. All-year physically active commuters had an overall more active PA pattern. The proportion fulfilling current PA recommendations varied substantially (1.4% to 92.2%) depending on data handling procedures and definition used. Twenty-eight percent was defined as having an “at-risk” behavior, which included both high sedentary time and low vigorous PA. In this large population-based sample, a majority of time was spent sedentary and only a fraction in vigorous PA, with clinically important variations between subgroups. This study provides important reference material and emphasizes the importance of a comprehensive assessment of all aspects of the individual PA pattern in future research and clinical practice.
20.	Franck, Niclas, et al. (författare) Identification of adipocyte genes regulated by caloric intake 2011 Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Endocrine society. - 0021-972X .- 1945-7197. ; 96:2, s. E413-E418 Tidskriftsartikel (refereegranskat)abstract CONTEXT: Changes in energy intake have marked and rapid effects on metabolic functions and some of the effects may be due to changes in adipose tissue gene expression that precede alterations in body weight. OBJECTIVE: To identify genes in adipose tissue regulated by changes in caloric intake independent of changes in body weight. RESEARCH DESIGN AND METHODS: Obese subjects were given a very-low calorie diet (VLCD; 450 kcal/day) for 16 weeks. After the diet, ordinary food was gradually reintroduced during 2 weeks while there were minimal changes in body weight. Adipose tissue gene expression was measured by microarray analysis. First, genes regulated during caloric restriction and in the opposite direction during the weight stable re-feeding phase were identified. To verify opposite regulation to that observed during caloric restriction, identified genes were further analyzed using adipocyte expression profiles from healthy subjects before and after overfeeding. Results were confirmed using real time PCR or immunoassay. RESULTS: Using a significance level of p<0.05 for all comparisons, 52 genes were downregulated and 50 were up-regulated by caloric restriction and regulated in the opposite direction by re-feeding and overfeeding. Among these were genes that affect lipogenesis (ACLY, ACACA, FASN, SCD), protein synthesis (4EBP1, 4EBP2), beta-oxidation (CPT1B), liberation of fatty acids (CIDEA) and glyceroneogenesis (PCK2). Interestingly, several of these are under control of the master regulator mTOR. CONCLUSIONS: The observed transcriptional changes indicate that mTOR plays a central role in the control of diet-regulated adipocyte genes involved in lipogenesis and protein synthesis.
21.	Fridén, Michael, et al. (författare) Hepatic Unsaturated Fatty Acids Are Linked to Lower Degree of Fibrosis in Non-alcoholic Fatty Liver Disease 2022 Ingår i: Frontiers in Medicine. - : Frontiers Media SA. - 2296-858X. ; 8 Tidskriftsartikel (refereegranskat)abstract Background: The hepatic lipidome of patients with early stages of non-alcoholic fatty liver disease (NAFLD) has been fairly well-explored. However, studies on more progressive forms of NAFLD, i.e., liver fibrosis, are limited. Materials and methods: Liver fatty acids were determined in cholesteryl esters (CE), phospholipids (PL), and triacylglycerols (TAG) by gas chromatography. Cross-sectional associations between fatty acids and biopsy-proven NAFLD fibrosis (n = 60) were assessed using multivariable logistic regression models. Stages of fibrosis were dichotomized into none-mild (F0–1) or significant fibrosis (F2–4). Models were adjusted for body-mass index (BMI), age and patatin-like phospholipase domain-containing protein 3 (PNPLA3 rs738409) (I148M) genotype. A secondary analysis examined whether associations from the primary analysis could be confirmed in the corresponding plasma lipid fractions. Results: PL behenic acid (22:0) was directly associated [OR (95% CI): 1.86 (1.00, 3.45)] whereas PL docosahexaenoic acid (22:6n-3) [OR (95% CI): 0.45 (0.23, 0.89)], TAG oleic acid (18:1n-9) [OR (95% CI): 0.52 (0.28, 0.95)] and 18:1n-9 and vaccenic acid (18:1n-7) (18:1) [OR (95% CI): 0.52 (0.28, 0.96)] were inversely associated with liver fibrosis. In plasma, TAG 18:1n-9 [OR (95% CI): 0.55 (0.31, 0.99)], TAG 18:1 [OR (95% CI): 0.54 (0.30, 0.97)] and PL 22:0 [OR (95% CI): 0.46 (0.25, 0.86)] were inversely associated with liver fibrosis. Conclusion: Higher TAG 18:1n-9 levels were linked to lower fibrosis in both liver and plasma, possibly reflecting an altered fatty acid metabolism. Whether PL 22:6n-3 has a protective role, together with a potentially adverse effect of hepatic 22:0, on liver fibrosis warrants large-scale studies.
22.	Gummesson, Anders, 1973, et al. (författare) Adipose tissue is not an important source for matrix metalloproteinase-9 in the circulation. 2009 Ingår i: Scandinavian journal of clinical and laboratory investigation. - 1502-7686 .- 0036-5513. ; 69:6, s. 636-42 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES: Matrix metalloproteinase 9 (MMP-9) is overexpressed in atherosclerotic plaques and in many cancers, and has emerged as a potential circulating biomarker for such diseases. However, adipose tissue (AT) might also produce circulating MMP-9, thereby reducing the value of MMP-9 as a biomarker. The aim of this study was to evaluate the impact of AT on circulating MMP-9, and if the metabolic syndrome might have a modifying effect. METHODS: Gene expression of MMP-9 was measured in AT, isolated adipocytes, atherosclerotic plaques, macrophages and various other human tissues using real-time PCR. Relationships between plasma MMP-9 (ELISA), adiposity, and metabolic syndrome were analyzed in a population-based cohort of 61-year-old men (n=513). Both AT mRNA levels and circulating levels of MMP-9 were measured in obese subjects (n=40) with and without the metabolic syndrome, treated with a weight-reducing diet. RESULTS: Bone marrow, atherosclerotic plaques and macrophages had considerably higher MMP-9 mRNA than subcutaneous AT and isolated adipocytes. Among the 61-year-old men, active plasma MMP-9 concentrations were associated with several metabolic syndrome factors, and inflammatory markers, but not body mass index (BMI). In obese patients with, but not without metabolic syndrome AT mRNA levels and circulating MMP-9 declined during weight reduction, but there was no association between changes in plasma MMP-9 and BMI. CONCLUSION: The results show that adipose tissue per se is not associated with circulating MMP-9. Components of the metabolic syndrome, such as circulating insulin and glucose were related to plasma MMP-9 both in the observation and dietary weight loss studies.
23.	Gummesson, Anders, 1973, et al. (författare) Intestinal Permeability Is Associated With Visceral Adiposity in Healthy Women. 2011 Ingår i: Obesity (Silver Spring, Md.). - : Wiley. - 1930-7381. Tidskriftsartikel (refereegranskat)abstract Increased visceral fat, as opposed to subcutaneous/gluteal, most strongly relates to key metabolic dysfunctions including insulin resistance, hepatic steatosis, and inflammation. Mesenteric fat hypertrophy in patients with Crohn's disease and in experimental rodent models of gut inflammation suggest that impaired gut barrier function with increased leakage of gut-derived antigens may drive visceral lipid deposition. The aim of this study was to determine whether increased intestinal permeability is associated with visceral adiposity in healthy humans. Normal to overweight female subjects were recruited from a population-based cohort. Intestinal permeability was assessed using the ratio of urinary excretion of orally ingested sucralose to mannitol (S/M). In study 1 (n = 67), we found a positive correlation between waist circumference and S/M excretion within a time frame of urine collection consistent with permeability of the lower gastrointestinal tract (6-9 hours post-ingestion; P = 0.022). These results were followed up in study 2 (n = 55) in which we used computed tomography and dual energy X-ray absorptiometry to measure visceral and subcutaneous fat areas of the abdomen, liver fat content, and total body fat of the same women. The S/M ratio from the 6-12 h urine sample correlated with visceral fat area (P = 0.0003) and liver fat content (P = 0.004), but not with subcutaneous or total body fat. This novel finding of an association between intestinal permeability and visceral adiposity and liver fat content in healthy humans suggests that impaired gut barrier function should be further explored as a possible mediator of excess visceral fat accumulation and metabolic dysfunction.
24.	Gummesson, Anders, 1973, et al. (författare) Non-alcoholic fatty liver disease is a strong predictor of coronary artery calcification in metabolically healthy subjects: A cross-sectional, population-based study in middle-aged subjects 2018 Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 13:8 Tidskriftsartikel (refereegranskat)abstract Objectives This study aims to estimate the relationship between non-alcoholic fatty liver disease (NAFLD) and measures of atherosclerotic cardiovascular disease (ASCVD), and to determine to what extent such relationships are modified by metabolic risk factors. The study was conducted in the population-based Swedish CArdioPulmonary bioImage Study (SCAPIS) pilot cohort (n = 1015, age 50-64 years, 51.2% women). NAFLD was defined as computed tomography liver attenuation <= 40 Hounsfield Units, excluding other causes of liver fat. Coronary artery calcification score (CACS) was assessed using the Agatston method. Carotid plaques and intima media thickness (IMT) were measured by ultrasound. Metabolic status was based on assessments of glucose homeostasis, serum lipids, blood pressure and inflammation. A propensity score model was used to balance NAFLD and non NAFLD groups with regards to potential confounders and associations between NAFLD status and ASCVD variables in relation to metabolic status were examined by logistic and generalized linear regression models. NAFLD was present in 106 (10.4%) of the subjects and strongly associated with obesity-related traits. NAFLD was significantly associated with CACS after adjustment for confounders and metabolic risk factors (OR 1.77, 95% CI 1.07-2.94), but not with carotid plaques and IMT. The strongest association between NAFLD and CACS was observed in subjects with few metabolic risk factors (n = 612 [60% of all] subjects with 0-1 out of 7 predefined metabolic risk factors; OR 5.94, 95% CI 2.13-16.6). NAFLD was independently associated with coronary artery calcification but not with measures of carotid atherosclerosis in this cohort. The association between NAFLD and CACS was most prominent in the metabolically healthy subjects.
25.	Gummesson, Anders, 1973 (författare) Pathogenesis of Obesity and Effects of Treatment. Clinical and Molecular Studies on Body Fat, Energy Balance, and Weight Loss. 2009 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Obesity is common and related to many health problems including various forms of cancer. The condition arises from the imbalance between food intake and energy expenditure, and is strongly influenced by genetic factors. Weight loss has several health benefits, but for many of the obesity-related diseases such as cancer, the impact of obesity treatment is not clarified. Unfortunately, weight loss is in most cases difficult to sustain, and obesity treatment today is insufficient. The adipose tissue and the gastrointestinal tract play active roles in the regulation of whole-body energy balance, and therapeutic targets for the treatment of obesity may be found within these sites. Also, these organs may be responsible for mediating some of the adverse effects of obesity. Special attention has been drawn to visceral adipose tissue, i.e. the fat surrounding the intestines, as being particularly harmful. The aim of this thesis was to increase our understanding of the mechanisms behind human obesity and the consequences of obesity treatment. We used population-based cross-sectional studies, as well as longitudinal intervention studies with short- and long-term weight loss. CIDEA and CIDEC are two genes with putative functions in adipose tissue, and we therefore studied their transcriptional regulation in relation to energy balance and body composition as an attempt to elucidate their role in human obesity. The genes were predominantly expressed in adipose tissue as compared to other human tissues, both CIDEA and CIDEC gene transcription were highly responsive to changes in energy availability, and CIDEA correlated with body fat and insulin levels. CIDEA expression also correlated with basal metabolic rate and uncoupling protein 1, suggesting a role in the regulation of energy expenditure. In gene silencing experiments in cultured adipocytes, we showed that CIDEC is involved in the regulation of basal as well as stimulated lipolysis, and mitochondrial fatty acid oxidation. Together, our results support a role of CIDEC and CIDEA in human obesity. There are indications that impaired intestinal barrier with increased passage of gut-derived antigens may drive visceral adipose tissue accumulation, and we therefore investigated if increased intestinal permeability is associated with visceral obesity in humans. Study subjects were recruited from a population-based cohort of Swedish women. Intestinal permeability was assessed using the urinary excretion of orally ingested sucralose and mannitol. We used computed tomography to measure visceral and liver fat. Intestinal permeability of the large intestine correlated with visceral fat area (P=0.0003) and liver fat content (P=0.004). The results indicate that gut leakiness should be further explored as a possible cause of visceral fat accumulation. The Swedish Obese Subjects (SOS) study in combination with the Swedish National Cancer Register makes it possible to, for the first time, study the effects of bariatric surgery on cancer incidence in a prospective, controlled study setting. The SOS study started in 1987 and involves severely obese subjects, 2010 of which underwent bariatric surgery, and 2037 contemporaneously matched obese controls who received conventional treatment. Bariatric surgery resulted in a sustained weight reduction, whereas the average weight change in the control group was minimal. In women, the number of first-time cancers during on average 11 years after inclusion was lower in the surgery group compared to the control group (HR= 0.58, 95% CI: 0.44-0.77, p<0.001). In men, we could not detect any difference between treatment groups (HR=0.97, p=0.91). In summary, the results of this thesis suggest that the CIDEA and CIDEC genes play a role in obesity, impaired intestinal barrier function contributes to visceral fat accumulation, and bariatric surgery reduces the risk of developing cancer in severely obese women.
26.	Gummesson, Anders, 1973, et al. (författare) Relations of Adipose Tissue Cell Death-Inducing DFFA-like Effector A Gene Expression to Basal Metabolic Rate, Energy Restriction and Obesity: Population-based and Dietary Intervention Studies. 2007 Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:12, s. 4759-65 Tidskriftsartikel (refereegranskat)abstract Context: Cell death-inducing DFFA-like effector A (CIDEA) could be a potential target for the treatment of obesity via the modulation of metabolic rate, based on the findings that CIDEA inhibits the brown adipose tissue uncoupling process in rodents. Objective: To investigate the putative link between CIDEA and basal metabolic rate in humans, and to further elucidate the role of CIDEA in human obesity. Design: We have explored CIDEA gene expression in adipose tissue in two different human studies: A cross-sectional and population-based study assessing body composition and metabolic rate (Mölndal Metabolic study, n=92), and a longitudinal intervention-study of obese subjects treated with a very low calorie diet (VLCD study, n=24). Results: The CIDEA gene was predominantly expressed in adipocytes as compared to other human tissues. CIDEA gene expression in adipose tissue was inversely associated with basal metabolic rate independently of body composition, age and gender (p=0.014). VLCD induced an increase in adipose tissue CIDEA expression (p<0.0001) with a subsequent decrease in response to refeeding (p<0.0001). Reduced CIDEA gene expression was associated with a high body fat content (p<0.0001) and with high insulin levels (p<0.01). No dysregulation of CIDEA expression was observed in individuals with the metabolic syndrome when compared with BMI-matched controls. In a separate sample of VLCD-treated subjects (n=10), uncoupling protein 1 expression was reduced during diet (p=0.0026) and inversely associated with CIDEA expression (p=0.0014). Conclusion: The findings are consistent with the concept that CIDEA plays a role in adipose tissue energy expenditure.
27.	Gummesson, Christina, et al. (författare) Entrustable professional activities (EPAs) for undergraduate medical education : development and exploration of social validity 2023 Ingår i: BMC Medical Education. - : BioMed Central (BMC). - 1472-6920. ; 23:1 Tidskriftsartikel (refereegranskat)abstract Background: The development of entrustable professional activities (EPAs) as a framework for work-based training and assessment in undergraduate medical education has become popular. EPAs are defined as units of a professional activity requiring adequate knowledge, skills, and attitudes, with a recognized output of professional labor, independently executable within a time frame, observable and measurable in its process and outcome, and reflecting one or more competencies. Before a new framework is implemented in a specific context, it is valuable to explore social validity, that is, the acceptability by relevant stakeholders.Aim: The aim of our work was to define Core EPAs for undergraduate medical education and further explore the social validity of the constructs.Method and material: In a nationwide collaboration, EPAs were developed using a modified Delphi procedure and validated according to EQual by a group consisting of teachers nominated from each of the seven Swedish medical schools, two student representatives, and an educational developer (n = 16). In the next step, social validity was explored in a nationwide survey. The survey introduced the suggested EPAs. For each EPA, the importance of the EPA was rated, as was the rater’s perception of the present graduates’ required level of supervision when performing the activity. Free-text comments were also included and analyzed.Results: Ten Core EPAs were defined and validated. The validation scores for EQual ranged from 4.1 to 4.9. The nationwide survey had 473 responders. All activities were rated as “important” by most responders, ranging from 54 to 96%. When asked how independent current graduates were in performing the ten activities, 6 to 35% reported “independent”. The three themes of the free text comments were: ‘relevant target areas and content’; ‘definition of the activities’; and ‘clinical practice and learning’.Conclusion: Ten Core EPAs were defined and assessed as relevant for Swedish undergraduate medical education. There was a consistent gap between the perceived importance and the certainty that the students could perform these professional activities independently at the time of graduation. These results indicate that the ten EPAs may have a role in undergraduate education by creating clarity for all stakeholders.
28.	Gummesson, Christina, et al. (författare) Släpp kontrollbehovet och låt studenterna skärpa sin förmåga och drivkraft - inquiry based learning 2008 Konferensbidrag (refereegranskat)
29.	Hjelmgren, Ola, et al. (författare) Beta-Cell Function, Self-rated Health, and Lifestyle Habits in 64-Year-Old Swedish Women with Metabolically Healthy Obesity Phenotype 2020 Ingår i: Journal of Obesity & Metabolic Syndrome. - : Korean Society for the Study of Obesity. - 2508-6235 .- 2508-7576. ; 29:1, s. 39-46 Tidskriftsartikel (refereegranskat)abstract Background: A subset of obese individuals do not present metabolic abnormalities that commonly define the metabolic syndrome (MetS). This is referred to as a metabolically healthy obese (MHO) phenotype. The aim of the present study was to evaluate the prevalence of the MHO phenotype and its relationship with beta cell dysfunction by measuring C-peptide and proinsulin, anthropometric-, metabolic- and lipid appearance, as well as lifestyle behaviors and self-rated health in a cohort of 64-year-old Swedish women. Methods: The National Cholesterol Education Program definition was used to assess MetS. We defined normal weight as body mass index (BMI) 18.5-24.9 kg/m(2) and obesity as BMI >= 30 kg/m(2) to categorize participants as metabolically healthy normal weight, MHO, and metabolically unhealthy obese. Results: The MHO phenotype represented 36.3% of obese participants and 16.3% of total participants. The MHO group were at greater risk of having proinsulin levels >11 pmol/L, indicating impaired beta cell function. Further, homeostatic model assessment for insulin resistance, fasting plasma levels of insulin, and C-peptide showed significant trends, with the MHO phenotype group having intermediate levels among three groups. Health behaviors such as leisure time physical activity and alcohol intake were also intermediate in individuals with the MHO phenotype. Conclusion: In this study, we demonstrate that over a third of the obese women in our sample were MHO. Further, women with the MHO phenotype showed intermediate profiles considering beta cell function and insulin resistance, as well as metabolic variables, and tended to rate their general health as worse than otherwise similar individuals of normal weight.
30.	Kos, K., et al. (författare) Regulation of the fibrosis and angiogenesis promoter SPARC/osteonectin in human adipose tissue by weight change, leptin, insulin, and glucose : Regulation of SPARC in human adipose tissue 2009 Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 58:8, s. 1780-8 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: Matricellular Secreted Protein, Acidic and Rich in Cysteine (SPARC), originally discovered in bone as osteonectin, is a mediator of collagen deposition and promotes fibrosis. Adipose tissue collagen has recently been found to be linked with metabolic dysregulation. Therefore, we tested the hypothesis that SPARC in human adipose tissue is influenced by glucose metabolism and adipokines. RESEARCH DESIGN AND METHODS: Serum and adipose tissue biopsies were obtained from morbidly obese nondiabetic subjects undergoing bariatric surgery and lean control subjects for analysis of metabolic markers, SPARC, and various cytokines (RT-PCR). Additionally, 24 obese subjects underwent a very-low-calorie diet of 1,883 kJ (450 kcal)/day for 16 weeks and serial subcutaneous-abdominal-adipose tissue (SCAT) biopsies (weight loss: 28 +/- 3.7 kg). Another six lean subjects underwent fast-food-based hyperalimentation for 4 weeks (weight gain: 7.2 +/- 1.6 kg). Finally, visceral adipose tissue explants were cultured with recombinant leptin, insulin, and glucose, and SPARC mRNA and protein expression determined by Western blot analyses. RESULTS: SPARC expression in human adipose tissue correlated with fat mass and was higher in SCAT. Weight loss induced by very-low-calorie diet lowered SPARC expression by 33% and increased by 30% in adipose tissue of subjects gaining weight after a fast-food diet. SPARC expression was correlated with leptin independent of fat mass and correlated with homeostasis model assessment-insulin resistance. In vitro experiments showed that leptin and insulin potently increased SPARC production dose dependently in visceral adipose tissue explants, while glucose decreased SPARC protein. CONCLUSIONS: Our data suggest that SPARC expression is predominant in subcutaneous fat and its expression and secretion in adipose tissue are influenced by fat mass, leptin, insulin, and glucose. The profibrotic effects of SPARC may contribute to metabolic dysregulation in obesity.
31.	Kotol, David, et al. (författare) Longitudinal Plasma Protein Profiling Using Targeted Proteomics and Recombinant Protein Standards 2020 Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 19:12, s. 4815-4825 Tidskriftsartikel (refereegranskat)abstract Spike-in of standards of known concentrations used in proteomics-based workflows is an attractive approach for both accurate and precise multiplexed protein quantification. Here, a quantitative method based on targeted proteomics analysis of plasma proteins using isotope-labeled recombinant standards originating from the Human Protein Atlas project has been established. The standards were individually quantified prior to being employed in the final multiplex assay. The assays are mainly directed toward actively secreted proteins produced in the liver, but may also originate from other parts of the human body. This study included 21 proteins classified by the FDA as either drug targets or approved clinical protein biomarkers. We describe the use of this multiplex assay for profiling a well-defined human cohort with sample collection spanning over a one-year period. Samples were collected at four different time points, which allowed for a longitudinal analysis to assess the variable plasma proteome within individuals. Two assays toward APOA1 and APOB had available clinical data, and the two assays were benchmarked against each other. The clinical assay is based on antibodies and shows high correlation between the two orthogonal methods, suggesting that targeted proteomics with highly parallel, multiplex analysis is an attractive alternative to antibody-based protein assays.
32.	Lakshmikanth, T., et al. (författare) Human Immune System Variation during 1 Year 2020 Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 32:3 Tidskriftsartikel (refereegranskat)abstract The human immune system varies extensively between individuals, but variation within individuals over time has not been well characterized. Systems-level analyses allow for simultaneous quantification of many interacting immune system components and the inference of global regulatory principles. Here, we present a longitudinal, systems-level analysis in 99 healthy adults 50 to 65 years of age and sampled every third month for 1 year. We describe the structure of interindividual variation and characterize extreme phenotypes along a principal cum. From coordinated measurement fluctuations, we infer relationships between 115 immune cell populations and 750 plasma proteins constituting the blood immune system. While most individuals have stable immune systems, the degree of longitudinal variability is an individual feature. The most variable individuals, in the absence of overt infections, exhibited differences in markers of metabolic health suggestive of a possible link between metabolic and immunologic homeostatic regulation.
33.	Lam, YY, et al. (författare) Role of the Gut in Visceral Fat Inflammation and Metabolic Disorders 2011 Ingår i: OBESITY. - 1930-7381. ; 19:11, s. 2113-2120 Forskningsöversikt (refereegranskat)
34.	Magnusson, Björn, 1976, et al. (författare) Cell death-inducing DFF45-like effector C is reduced by caloric restriction and regulates adipocyte lipid metabolism. 2008 Ingår i: Metabolism: clinical and experimental. - : Elsevier BV. - 1532-8600. ; 57:9, s. 1307-13 Tidskriftsartikel (refereegranskat)abstract Members of the cell death-inducing DFF45-like effector (CIDE) gene family have been shown to regulate lipid metabolism. In this article, we report that the third member of the human CIDE family, CIDEC, is down-regulated in response to a reduced caloric intake. The down-regulation was demonstrated by microarray and real-time polymerase chain reaction analysis of subcutaneous adipose tissue in 2 independent studies on obese patients undergoing treatment with a very low calorie diet. By analysis of CIDEC expression in 65 human tissues, we conclude that human CIDEC is predominantly expressed in subcutaneous adipocytes. Together, these observations led us to investigate the effect of decreased CIDEC expression in cultured 3T3-L1 adipocytes. Small interfering RNA-mediated knockdown of CIDEC resulted in an increased basal release of nonesterified fatty acids, decreased responsiveness to adrenergic stimulation of lipolysis, and increased oxidation of endogenous fatty acids. Thus, we suggest that CIDEC is a regulator of adipocyte lipid metabolism and may be important for the adipocyte to adapt to changes in energy availability.
35.	Molnar, David, et al. (författare) Pre-diabetes is associated with attenuation rather than volume of epicardial adipose tissue on computed tomography 2023 Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 13:1 Tidskriftsartikel (refereegranskat)abstract The volume of epicardial adipose tissue (EATV) is increased in type-2 diabetes (T2D), while its attenuation (EATA) appears to be decreased. Similar patterns have been suggested in pre-diabetes, but data is scarce. In both pre-diabetes and T2D, any independent role of EATV and EATA in disease development remains to be proven, a task complicated by their substantial co-variation with other anthropometrics, e.g. BMI, waist circumference, and abdominal visceral adipose tissue (VAT). EATV and EATA was quantified in computed tomography (CT) images in a population study (n = 1948) using an automatic technique. Data was available on BMI, waist circumference, abdominal visceral adipose tissue (VAT) area, insulin resistance (IR) and glucose tolerance, the latter ranging from normal (NGT), over pre-diabetes (impaired fasting glucose [IFG, n = 414] impaired glucose tolerance [IGT, n = 321] and their combination [CGI, n = 128]), to T2D. EATV was increased in pre-diabetes, T2D and IR in univariable analyses and when adjusting for BMI, however not when adjusting for waist or VAT. EATA was reduced in pre-diabetes, T2D and IR in univariable analyses and when adjusting for BMI and waist, however not when adjusting for VAT. Adjustment for other co-variates had little influence on the results. In conclusion, EATV is increased and EATA reduced in pre-diabetes, T2D and IR, however, significant co-variation with other anthropometrics, especially VAT, obscures their function in disease development. The current results do not exclude a pathophysiological role of epicardial fat, but future studies need to adjust for anthropometrics, or focus on the microenvironment within the pericardial sac.
36.	Neiman, Maja, 1983-, et al. (författare) Individual and stable autoantibody repertoires in healthy individuals 2019 Ingår i: Autoimmunity. - : TAYLOR & FRANCIS LTD. - 0891-6934 .- 1607-842X. ; 52:1, s. 1-11 Tidskriftsartikel (refereegranskat)abstract In the era towards precision medicine, we here present the individual specific autoantibody signatures of 193 healthy individuals. The self-reactive IgG signatures are stable over time in a way that each individual profile is recognized in longitudinal sampling. The IgG autoantibody reactivity towards an antigen array comprising 335 protein fragments, representing 204 human proteins with potential relevance to autoimmune disorders, was measured in longitudinal plasma samples from 193 healthy individuals. This analysis resulted in unique autoantibody barcodes for each individual that were maintained over one year's time. The reactivity profiles, or signatures, are person specific in regards to the number of reactivities and antigen specificity. Two independent data sets were consistent in that each healthy individual displayed reactivity towards 0-16 antigens, with a median of six. Subsequently, four selected individuals were profiled on in-house produced high-density protein arrays containing 23,000 protein fragments representing 14,000 unique protein coding genes. Based on a unique, broad and deep longitudinal profiling of autoantibody reactivities, our results demonstrate a unique autoreactive profile in each analyzed healthy individual. The need and interest for broad-ranged and high-resolution molecular profiling of healthy individuals is rising. We have here generated and assessed an initial perspective on the global distribution of the self-reactive IgG repertoire in healthy individuals, by investigating 193 well-characterized healthy individuals.
37.	Olson, Fredrik J., 1975, et al. (författare) Circulating matrix metalloproteinase 9 levels in relation to sampling methods, femoral and carotid atherosclerosis. 2008 Ingår i: Journal of internal medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 263:6, s. 626-35 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES: To examine whether circulating levels of matrix metalloproteinase 9 (MMP-9) were associated with ultrasound-assessed intima-media thickness (IMT) and echolucent plaques in the carotid and femoral arteries. To examine preanalytical sources of variability in MMP-9 concentrations related to sampling procedures. SUBJECTS AND DESIGN: Plasma and serum MMP-9 levels were compared with ultrasound assessed measures of femoral and carotid atherosclerosis, in a cross-sectional study of 61-year-old men (n = 473). Preanalytical sources of variability in MMP-9 levels were examined in 10 healthy subjects. Main outcome measures were circulating levels of MMP-9 in serum and plasma, IMT of the carotid and femoral arteries, and plaque status based on size and echolucency. SETTING: Research unit at university hospital. RESULTS: Plasma concentrations of total and active MMP-9 were associated with femoral artery IMT independently of traditional cardiovascular risk factors, and were higher in subjects with moderate to large femoral plaques. Plasma MMP-9 concentration was higher in men with echolucent femoral plaques (P = 0.006) compared with subjects without femoral plaques. No similar associations were found for carotid plaques. MMP-9 concentrations were higher in serum than in plasma, and higher when sampling was performed with Vacutainer than with syringe. MMP-9 levels in serum were more strongly associated with peripheral neutrophil count compared with MMP-9 levels in plasma. CONCLUSIONS: Plasma MMP-9 levels were associated with atherosclerosis in the femoral artery, and total MMP-9 concentration was higher in men with echolucent femoral plaques. The choice of sample material and sampling method affect the measurements of circulating MMP-9 levels.
38.	Olsson, Lisa M., 1984, et al. (författare) Dynamics of the normal gut microbiota: A longitudinal one-year population study in Sweden 2022 Ingår i: Cell Host and Microbe. - : Elsevier BV. - 1931-3128 .- 1934-6069. ; 30:5 Tidskriftsartikel (refereegranskat)abstract Temporal dynamics of the gut microbiota potentially limit the identification of microbial features associated with health status. Here, we used whole-genome metagenomic and 16S rRNA gene sequencing to characterize the intra- and inter-individual variations of gut microbiota composition and functional potential of a disease-free Swedish population (n = 75) over one year. We found that 23% of the total compositional variance was explained by intra-individual variation. The degree of intra-individual compositional variability was negatively associated with the abundance of Faecalibacterium prausnitzii (a butyrate producer) and two Bifidobacterium species. By contrast, the abundance of facultative anaerobes and aerotolerant bacteria such as Escherichia coli and Lactobacillus acidophilus varied extensively, independent of compositional stability. The contribution of intra-individual variance to the total variance was greater for functional pathways than for microbial species. Thus, reliable quantification of microbial features requires repeated samples to address the issue of intra-individual variations of the gut microbiota.
39.	Palming, Jenny, 1975, et al. (författare) The expression of NAD(P)H:quinone oxidoreductase 1 is high in human adipose tissue, reduced by weight loss, and correlates with adiposity, insulin sensitivity, and markers of liver dysfunction. 2007 Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:6, s. 2346-52 Tidskriftsartikel (refereegranskat)abstract CONTEXT: We have previously identified nicotinamide adenine dinucleotide phosphate:quinone oxidoreductase 1 (NQO1), an enzyme involved in the protection against oxidative stress, as a gene predominantly expressed in human adipocytes. Studies in mice deficient in NQO1 activity suggest that NQO1 may also play an important role in metabolism. OBJECTIVE: The aim of this study was to explore the expression and regulation of NQO1 in human adipose tissue (AT) and isolated adipocytes. PATIENTS AND RESULTS: The high expression of NQO1 in adipocytes was verified in human adipocytes and AT by real-time PCR. DNA microarray analysis showed that NQO1 was expressed at higher levels in large compared with small adipocytes, isolated from the same fat biopsy. Furthermore, NQO1 mRNA levels were positively correlated with adipocyte size (n = 7; P < 0.002). During an 18-wk diet regime (n = 24; mean weight loss 27 kg), the NQO1 expression in human sc AT was down-regulated (P < 0.0001), and mRNA levels correlated with body mass index (P = 0.0005), sc, and total abdominal AT areas, as determined by computerized tomography (P < 0.0001, both) and metabolic parameters. NQO1 mRNA levels were also positively correlated with aspartate aminotransferase (P = 0.0028) and alanine aminotransferase (P = 0.0219), markers known to be associated with severity of hepatic steatosis. CONCLUSIONS: NQO1 is highly expressed in human AT, particularly in large adipocytes. AT NQO1 expression is reduced during diet-induced weight loss, and the expression levels positively correlate with adiposity, glucose tolerance, and markers of liver dysfunction. Together, these findings indicate a role for NQO1 in the metabolic complications of human obesity.
40.	Pattanaik, Bagmi, 1977, et al. (författare) Polymorphisms in alpha 7 nicotinic acetylcholine receptor gene, CHRNA7, and its partially duplicated gene, CHRFAM7A, associate with increased inflammatory response in human peripheral mononuclear cells 2022 Ingår i: Faseb Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 36:5 Tidskriftsartikel (refereegranskat)abstract The vagus nerve can, via the alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR), regulate inflammation. The gene coding for the alpha 7nAChR, CHRNA7, can be partially duplicated, that is, CHRFAM7A, which is reported to impair the anti-inflammatory effect mediated via the alpha 7nAChR. Several single nucleotide polymorphisms (SNPs) have been described in both CHRNA7 and CHRFAM7A, however, the functional role of these SNPs for immune responses remains to be investigated. In the current study, we set out to investigate whether genetic variants of CHRNA7 and CHRFAM7A can influence immune responses. By investigating data available from the Swedish SciLifeLab SCAPIS Wellness Profiling (S3WP) study, in combination with droplet digital PCR and freshly isolated PBMCs from the S3WP participants, challenged with lipopolysaccharide (LPS), we show that CHRNA7 and CHRFAM7A are expressed in human PBMCs, with approximately four times higher expression of CHRFAM7A compared with CHRNA7. One SNP in CHRFAM7A, rs34007223, is positively associated with hsCRP in healthy individuals. Furthermore, gene ontology (GO)-terms analysis of plasma proteins associated with gene expression of CHRNA7 and CHRFAM7A demonstrated an involvement for these genes in immune responses. This was further supported by in vitro data showing that several SNPs in both CHRNA7 and CHRFAM7A are significantly associated with cytokine response. In conclusion, genetic variants of CHRNA7 and CHRFAM7A alters cytokine responses. Furthermore, given that CHRFAM7A SNP rs34007223 is associated with inflammatory marker hsCRY in healthy individuals suggests that CHRFAM7A may have a more pronounced role in regulating inflammatory processes in humans than previously been recognized.
41.	Rosqvist, Fredrik, 1985-, et al. (författare) Fatty acids in multiple circulating lipid fractions reflects the composition of liver triglycerides in humans 2022 Ingår i: Clinical Nutrition. - : Elsevier BV. - 1532-1983 .- 0261-5614. ; 41:4, s. 805-809 Tidskriftsartikel (refereegranskat)abstract Background and aims: Fatty acids (e.g. 16:1n-7) and desaturase indices (e.g. stearoyl-CoA desaturase, SCD) in plasma cholesteryl esters (CE) and phospholipids (PL) are used as biomarkers of dietary fat quality and lipid metabolism and are associated with disease outcomes. Endogenously produced circulating fatty acids are believed to reflect composition of the liver, yet little data exist to support such relationship. We investigated associations between circulating fatty acids and fatty acids within the liver. Methods: Liver biopsies and blood were collected from n = 60 patients with non-alcoholic fatty liver disease. Fatty acids in CE, PL and triglycerides (TG) in plasma and liver were analyzed using gas chromatography. Associations were assessed using Spearman rank correlations. Results: Overall, fatty acids and desaturase indices in plasma PL and TG showed moderate–strong correlations with fatty acids and desaturase indices in corresponding lipid fractions in liver. For plasma CE, 16:1n-7 and SCD were correlated with 16:1n-7 and SCD in liver CE. Noteworthy, fatty acids in plasma CE and PL also showed moderate–strong correlations with fatty acids in liver TG (e.g. r = 0.82–0.87 for 16:1n-7 and r = 0.77 for SCD). Conclusion: We demonstrate that fatty acids in circulating lipid fractions, including CE, TG and PL, reflects the composition of liver TG in humans, suggesting that circulating fatty acids might be useful biomarkers for the fatty acid composition of the liver. As liver tissue is rarely available in cohort studies, our findings could enhance our understanding of plasma fatty acids as markers of hepatic lipid metabolism and their links to metabolic diseases.
42.	Roswall, Josefine, et al. (författare) Developmental trajectory of the healthy human gut microbiota during the first 5 years of life 2021 Ingår i: Cell Host & Microbe. - : Elsevier BV. - 1931-3128 .- 1934-6069. ; 29:5 Tidskriftsartikel (refereegranskat)abstract The gut is inhabited by a densely populated ecosystem, the gut microbiota, that is established at birth. However, the succession by which different bacteria are incorporated into the gut microbiota is still relatively unknown. Here, we analyze the microbiota from 471 Swedish children followed from birth to 5 years of age, collecting samples after 4 and 12 months and at 3 and 5 years of age as well as from their mothers at birth using 16S rRNA gene profiling. We also compare their microbiota to an adult Swedish population. Genera follow 4 different colonization patterns during establishment where Methanobrevibacter and Christensenellaceae colonize late and do not reached adult levels at 5 years. These late colonizers correlate with increased alpha diversity in both children and adults. By following the children through age-specific community types, we observe that children have individual dynamics in the gut microbiota development trajectory.
43.	Royer, Patrick, et al. (författare) Large-scale plasma proteomics in the UK Biobank modestly improves prediction of major cardiovascular events in a population without previous cardiovascular disease 2024 Ingår i: EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY. - 2047-4873 .- 2047-4881. Tidskriftsartikel (refereegranskat)abstract [ ' A i m s I m p r o v e d i d e n t i f i c a t i o n o f i n d i v i d u a l s a t h i g h r i s k o f d e v e l o p i n g c a r d i o v a s c u l a r d i s e a s e w o u l d e n a b l e t a r g e t e d i n t e r v e n t i o n s a n d p o t e n t i a l l y l e a d t o r e d u c t i o n s i n m o r t a l i t y a n d m o r b i d i t y . O u r a i m w a s t o d e t e r m i n e w h e t h e r u s e o f l a r g e - s c a l e p r o t e o m i c s i m p r o v e s p r e d i c t i o n o f c a r d i o v a s c u l a r e v e n t s b e y o n d t r a d i t i o n a l r i s k f a c t o r s ( T R F s ) . M e t h o d s a n d r e s u l t s U s i n g p r o x i m i t y e x t e n s i o n a s s a y s , 2 9 1 9 p l a s m a p r o t e i n s w e r e m e a s u r e d i n 3 8 3 8 0 p a r t i c i p a n t s o f t h e U K B i o b a n k . B o t h d a t a - a n d l i t e r a t u r e - b a s e d f e a t u r e s e l e c t i o n a n d t r a i n e d m o d e l s u s i n g e x t r e m e g r a d i e n t b o o s t i n g m a c h i n e l e a r n i n g w e r e u s e d t o p r e d i c t r i s k o f m a j o r c a r d i o v a s c u l a r e v e n t s ( M A C E s : f a t a l a n d n o n - f a t a l m y o c a r d i a l i n f a r c t i o n , s t r o k e , a n d c o r o n a r y a r t e r y r e v a s c u l a r i z a t i o n ) d u r i n g a 1 0 - y e a r f o l l o w - u p . A r e a u n d e r t h e c u r v e ( A U C ) a n d n e t r e c l a s s i f i c a t i o n i n d e x ( N R I ) w e r e u s e d t o e v a l u a t e t h e a d d i t i v e v a l u e o f s e l e c t e d p r o t e i n p a n e l s t o M A C E p r e d i c t i o n b y S y s t e m a t i c C O r o n a r y R i s k E v a l u a t i o n 2 ( S C O R E 2 ) o r t h e 1 0 T R F s u s e d i n S C O R E 2 . S C O R E 2 a n d S C O R E 2 r e f i t t e d t o U K B i o b a n k d a t a p r e d i c t e d M A C E w i t h A U C s o f 0 . 7 4 0 a n d 0 . 7 4 9 , r e s p e c t i v e l y . D a t a - d r i v e n s e l e c t i o n i d e n t i f i e d 1 1 4 p r o t e i n s o f g r e a t e s t r e l e v a n c e f o r p r e d i c t i o n . P r e d i c t i o n o f M A C E w a s n o t i m p r o v e d b y u s i n g t h e s e p r o t e i n s a l o n e ( A U C o f 0 . 7 5 8 ) b u t w a s s i g n i f i c a n t l y i m p r o v e d b y c o m b i n i n g t h e s e p r o t e i n s w i t h S C O R E 2 o r t h e 1 0 T R F s ( A U C = 0 . 7 7 1 , P < 0 0 1 , N R I = 0 . 1 4 0 , a n d A U C = 0 . 7 6 7 , P = 0 . 0 3 , N R I 0 . 0 5 3 , r e s p e c t i v e l y ) . L i t e r a t u r e - b a s e d p r o t e i n s e l e c t i o n ( 1 1 3 p r o t e i n s f r o m f i v e p r e v i o u s s t u d i e s ) a l s o i m p r o v e d r i s k p r e d i c t i o n b e y o n d T R F s w h i l e a r a n d o m s e l e c t i o n o f 1 1 4 p r o t e i n s d i d n o t . C o n c l u s i o n L a r g e - s c a l e p l a s m a p r o t e o m i c s w i t h d a t a - d r i v e n a n d l i t e r a t u r e - b a s e d p r o t e i n s e l e c t i o n m o d e s t l y i m p r o v e s p r e d i c t i o n o f f u t u r e M A C E b e y o n d T R F s . L a y s u m m a r y T h e r i s k o f h a v i n g a m y o c a r d i a l i n f a r c t i o n o r s t r o k e i s u s u a l l y a s s e s s e d b y c l i n i c a l s c o r e s i n c l u d i n g t r a d i t i o n a l r i s k f a c t o r s f o r c a r d i o v a s c u l a r d i s e a s e . T h e d e v e l o p m e n t o f n e w t e c h n o l o g i e s e n a b l e s t h e r a p i d m e a s u r e m e n t o f a n i n c r e a s i n g n u m b e r o f b l o o d p r o t e i n s . I n t h i s s t u d y , w e a p p l i e d m a c h i n e l e a r n i n g t e c h n i q u e s i n a U K - b a s e d c o h o r t o f 3 8 3 8 0 p a r t i c i p a n t s w i t h 2 9 1 9 b l o o d p r o t e i n s m e a s u r e d . W e o b t a i n e d a s e t o f 1 1 4 p r o t e i n s t h a t i m p r o v e d t h e p r e d i c t i o n o f t h e 1 0 - y e a r r i s k o f m a j o r c a r d i o v a s c u l a r e v e n t w h e n a d d e d t o t r a d i t i o n a l r i s k f a c t o r s . I m p r o v e m e n t s w e r e a l s o a c h i e v e d u s i n g a s e t o f 1 1 3 p r o t e i n s f o u n d i n p r e v i o u s s t u d i e s . H o w e v e r , t h e m a g n i t u d e o f t h e s e i m p r o v e m e n t s w a s r e l a t i v e l y l o w a n d t h e c l i n i c a l u t i l i t y o f c o m b i n i n g t h e s e p r o t e i n s w i t h t r a d i t i o n a l r i s k f a c t o r s i n p r i m a r y p r e v e n t i o n w i l l h a v e t o b e f u r t h e r i n v e s t i g a t e d . ' , ' [ G R A P H I C S ] ' , ' . ' ]
44.	Royer, Patrick, et al. (författare) Plasma proteomics for prediction of subclinical coronary artery calcifications in primary prevention 2024 Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 271, s. 55-67 Tidskriftsartikel (refereegranskat)abstract Background and aims: Recent developments in high-throughput proteomic technologies enable the discovery of novel biomarkers of coronary atherosclerosis. The aims of this study were to test if plasma protein subsets could detect coronary artery calcifications (CAC) in asymptomatic individuals and if they add predictive value beyond traditional risk factors. Methods: Using proximity extension assays, 1,342 plasma proteins were measured in 1,827 individuals from the Impaired Glucose Tolerance and Microbiota (IGTM) study and 883 individuals from the Swedish Cardiopulmonary BioImage Study (SCAPIS) aged 50-64 years without history of ischaemic heart disease and with CAC assessed by computed tomography. After data-driven feature selection, extreme gradient boosting machine learning models were trained on the IGTM cohort to predict the presence of CAC using combinations of proteins and traditional risk factors. The trained models were validated in SCAPIS. Results: The best plasma protein subset (44 proteins) predicted CAC with an area under the curve (AUC) of 0.691 in the validation cohort. However, this was not better than prediction by traditional risk factors alone (AUC = 0.710, P = .17). Adding proteins to traditional risk factors did not improve the predictions (AUC = 0.705, P = .6). Most of these 44 proteins were highly correlated with traditional risk factors. Conclusions: A plasma protein subset that could predict the presence of subclinical CAC was identified but it did not outperform nor improve a model based on traditional risk factors. Thus, support for this targeted proteomics platform to predict subclinical CAC beyond traditional risk factors was not found.
45.	Saiki, Atsuhito, et al. (författare) Tenomodulin is highly expressed in adipose tissue, increased in obesity, and down-regulated during diet-induced weight loss. 2009 Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 94:10, s. 3987-94 Tidskriftsartikel (refereegranskat)abstract CONTEXT: Tenomodulin (TNMD), a putative angiogenesis inhibitor, is expressed in hypovascular connective tissues. Global gene expression scans show that the TNMD gene also is expressed in human adipose tissue and that its expression is regulated in response to weight reduction; however, more detailed information is lacking. OBJECTIVE: The aim of this study was to investigate TNMD tissue distribution and TNMD gene expression in human adipose tissue in relation to obesity and metabolic disease. DESIGN, PATIENTS, AND INTERVENTIONS: TNMD gene expression, tissue distribution, and TNMD gene expression in adipose tissue from different depots, from lean and obese subjects, and during diet-induced weight reduction were analyzed by DNA microarray and real-time PCR. MAIN OUTCOME MEASURE: We primarily measured TNMD gene expression. RESULTS: The TNMD gene was predominantly expressed in sc adipose tissue. TNMD gene expression was higher in sc than omental adipose tissue both in lean (P = 0.002) and obese subjects (P = 0.014). In both women and men, TNMD gene expression was significantly higher in the obese subjects compared to the lean subjects (P = 1.1 x 10(-26) and P = 0.010, respectively). In a multiple linear regression analysis, BMI was a significant independent predictor of TNMD gene expression. TNMD gene expression was down-regulated during diet-induced weight loss, with a 65% decrease after 18 wk of diet (P < 0.0001). CONCLUSIONS: We conclude that human adipose tissue TNMD gene expression is highly affected by obesity, adipose tissue location, and weight loss, indicating that TNMD may play a role in adipose tissue function.
46.	Schmidt, Caroline, 1966, et al. (författare) Psychosocial work conditions and prediabetes risks: a cross-sectional study in middle-aged men and women. 2023 Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 13:1 Tidskriftsartikel (refereegranskat)abstract Prediabetes is a condition between diabetes and normoglycemia, and is a state of major health concern, as a large proportion of people with prediabetes are likely to develop diabetes which is associated with high mortality and morbidity. The purpose of this study was to investigate whether adverse psychosocial work conditions, based on the Job Demand-Control-social support model, increases risk for early dysregulated glucose metabolism in 50-64-year-old men and women. Job conditions were measured with the Swedish Demand-Control-Support questionnaire. Impaired glucose metabolism was assessed by an oral glucose tolerance test. Differences between groups were analyzed with Chi-square test and one-way ANOVA with Bonferroni post-hoc test. Odds ratios (OR) and 95% confidence intervals (95% CI) between Job Demand-control-support and prediabetes outcome were calculated with multiple logistic regression. Results from an adjusted logistic regression model showed that in men and woman separately, an active work situation (high demands-high control) was associated with significantly lower prediabetes risk (OR 0.657, 95% CI 0.513-0.842). This finding is consistent through all logistic regression models with different levels of adjustments. Further, the current study does not lend support for the hypothesis that work conditions characterized by high demands-low control were associated with dysregulated glucose metabolism in men nor women despite accumulation of many life-style related risk factors in the high strain group. In conclusion, we could show that men and women assessing their work conditions as active, had lower risk for prediabetes.
47.	Sjöholm, Kajsa, 1971, et al. (författare) A microarray search for genes predominantly expressed in human omental adipocytes: adipose tissue as a major production site of serum amyloid A. 2005 Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 90:4, s. 2233-9 Tidskriftsartikel (refereegranskat)abstract To identify genes predominantly expressed in omental adipocytes, microarray expression profiles from 33 human tissues or cell types were analyzed, using an algorithm developed for identification of transcripts predominantly expressed in a certain tissue. Both known adipocyte-specific and more unexpected genes were among the 28 genes identified. To validate the approach, adipocyte expression of three of these genes, acute-phase serum amyloid A (A-SAA), aquaporin 7, and transport secretion protein-2.2, was compared with 17 other human tissues by real-time PCR. The unexpectedly high expression of A-SAA in adipocytes was further verified by Northern blot and immunohistochemistry. The liver, reported to be the main production site for A-SAA, displayed the second highest expression using microarray and real-time PCR. In obese subjects, adipose tissue mRNA and serum A-SAA levels were down-regulated during an 18-wk diet regime (P < 0.05 and P < 0.0001, respectively). A-SAA serum levels were highly correlated to adipose tissue mRNA levels (P < 0.001) and to the total (P < 0.0001) and sc (P < 0.0001) adipose tissue areas, as analyzed by computed tomography. We show that adipose tissue is a major expression site of A-SAA during the nonacute-phase reaction condition. This provides a direct link between adipose tissue mass and a marker for low-grade inflammation and cardiovascular risk.
48.	Sjöström, Lars, et al. (författare) Effects of bariatric surgery on cancer incidence in obese patients in Sweden (Swedish Obese Subjects Study): a prospective, controlled intervention trial. 2009 Ingår i: The lancet oncology. - 1474-5488. ; 10:7, s. 653-62 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Obesity is a risk factor for cancer. Intentional weight loss in the obese might protect against malignancy, but evidence is limited. To our knowledge, the Swedish Obese Subjects (SOS) study is the first intervention trial in the obese population to provide prospective, controlled cancer-incidence data. METHODS: The SOS study started in 1987 and involved 2010 obese patients (body-mass index [BMI] >or=34 kg/m(2) in men, and >or=38 kg/m(2) in women) who underwent bariatric surgery and 2037 contemporaneously matched obese controls, who received conventional treatment. While the main endpoint of SOS was overall mortality, the main outcome of this exploratory report was cancer incidence until Dec 31, 2005. Cancer follow-up rate was 99.9% and the median follow-up time was 10.9 years (range 0-18.1 years). FINDINGS: Bariatric surgery resulted in a sustained mean weight reduction of 19.9 kg (SD 15.6 kg) over 10 years, whereas the mean weight change in controls was a gain of 1.3 kg (SD 13.7 kg). The number of first-time cancers after inclusion was lower in the surgery group (n=117) than in the control group (n=169; HR 0.67, 95% CI 0.53-0.85, p=0.0009). The sex-treatment interaction p value was 0.054. In women, the number of first-time cancers after inclusion was lower in the surgery group (n=79) than in the control group (n=130; HR 0.58, 0.44-0.77; p=0.0001), whereas there was no effect of surgery in men (38 in the surgery group vs 39 in the control group; HR 0.97, 0.62-1.52; p=0.90). Similar results were obtained after exclusion of all cancer cases during the first 3 years of the intervention. INTERPRETATION: Bariatric surgery was associated with reduced cancer incidence in obese women but not in obese men. FUNDING: Swedish Research Council, Swedish Foundation for Strategic Research, Swedish Federal Government under the LUA/ALF agreement, Hoffmann La Roche, Cederoths, AstraZeneca, Sanofi-Aventis, Ethicon Endosurgery.
49.	Sjöström, Lars, et al. (författare) Effects of bariatric surgery on mortality in Swedish obese subjects. 2007 Ingår i: The New England journal of medicine. - 1533-4406. ; 357:8, s. 741-52 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Obesity is associated with increased mortality. Weight loss improves cardiovascular risk factors, but no prospective interventional studies have reported whether weight loss decreases overall mortality. In fact, many observational studies suggest that weight reduction is associated with increased mortality. METHODS: The prospective, controlled Swedish Obese Subjects study involved 4047 obese subjects. Of these subjects, 2010 underwent bariatric surgery (surgery group) and 2037 received conventional treatment (matched control group). We report on overall mortality during an average of 10.9 years of follow-up. At the time of the analysis (November 1, 2005), vital status was known for all but three subjects (follow-up rate, 99.9%). RESULTS: The average weight change in control subjects was less than +/-2% during the period of up to 15 years during which weights were recorded. Maximum weight losses in the surgical subgroups were observed after 1 to 2 years: gastric bypass, 32%; vertical-banded gastroplasty, 25%; and banding, 20%. After 10 years, the weight losses from baseline were stabilized at 25%, 16%, and 14%, respectively. There were 129 deaths in the control group and 101 deaths in the surgery group. The unadjusted overall hazard ratio was 0.76 in the surgery group (P=0.04), as compared with the control group, and the hazard ratio adjusted for sex, age, and risk factors was 0.71 (P=0.01). The most common causes of death were myocardial infarction (control group, 25 subjects; surgery group, 13 subjects) and cancer (control group, 47; surgery group, 29). CONCLUSIONS: Bariatric surgery for severe obesity is associated with long-term weight loss and decreased overall mortality.
50.	Stanne, Tara M, 1979, et al. (författare) A Genome-wide Study of Common and Rare Genetic Variants Associated with Circulating Thrombin Activatable Fibrinolysis Inhibitor 2018 Ingår i: Thrombosis and Haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 118:2, s. 298-308 Tidskriftsartikel (refereegranskat)abstract Thrombin-activatable fibrinolysis inhibitor (TAFI) plays a central role in haemostasis, and plasma TAFI concentrations are heritable. Candidate gene studies have identified several variants within the gene encoding TAFI, CPB2, that explain part of the estimated heritability. Here, we describe an exploratory genome-wide association study to identify novel variants within and outside of the CPB2 locus that influence plasma concentrations of intact TAFI and/or the extent of TAFI activation (measured by released TAFI activation peptide, TAFI-AP) amongst 3,260 subjects from Southern Sweden. We also explored the role of rare variants on the HumanExome BeadChip. We confirmed the association with previously reported common variants in CPB2 for both intact TAFI and TAFI-AP, and discovered novel associations with variants in putative CPB2 enhancers. We identified a gene-based association with intact TAFI at CPB2 (PSKAT-O = 2.8 x 10(-8)), driven by two novel rare nonsynonymous single nucleotide polymorphisms (SNPs; I420N and D177G). Carriers of the rare variant of D177G (rs140446990; MAF 0.2%) had lower intact TAFI and TAFI-AP concentrations compared with non-carriers (intact TAFI, geometricmean 53 vs. 78%, PT-test < 5 x 10(-7); TAFI-AP 63 vs. 99%, P(T-tes)t = 7.2 x 10(-4)). For TAFI-AP, we identified a genome-wide significant association at an intergenic region of chromosome 3p14.1 and five gene-based associations (all PSKAT-O = 5 x 10(-6)). Using well-characterized assays together with a genome-wide association study and a rare-variant approach, we verified CPB2 to be the primary determinant of TAFI concentrations and identified putative secondary loci (candidate variants and genes) associated with intact TAFI and TAFI-AP that require independent validation.

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Typ av publikation: tidskriftsartikel (51); konferensbidrag (5); forskningsöversikt (2); doktorsavhandling (1); bokkapitel (1)

Typ av innehåll: refereegranskat (56); övrigt vetenskapligt/konstnärligt (4)

Författare/redaktör: Gummesson, Anders, 1 ... (45); Bergström, Göran, 19 ... (21); Carlsson, Lena M S, ... (15); Uhlén, Mathias (13); Fagerberg, Linn (10); Gummesson, Anders (10); visa fler...; Carlsson, Björn, 195 ... (10); Bäckhed, Fredrik, 19 ... (9); Schmidt, Caroline, 1 ... (8); Lystig, Ted (8); Edfors, Fredrik (7); Fagerberg, Björn, 19 ... (7); Svensson, Per-Arne, ... (7); Sjöholm, Kajsa, 1971 (7); Zhong, Wen (6); Engström, Gunnar (5); Schwenk, Jochen M. (5); Adiels, Martin, 1976 (5); Björnson, Elias, 198 ... (5); Gummesson, Christina (5); Sjöström, Lars (5); Wanders, Alkwin (5); Schultheis, Christia ... (5); Hjelmgren, Ola (5); Olsson, Lisa M., 198 ... (4); Tremaroli, Valentina ... (4); Forsström, Björn (4); Nilsson, Peter (4); Rosengren, Annika, 1 ... (4); Jacobson, Peter, 196 ... (4); Olsson, Bob, 1969 (4); Hagström, Emil (4); Jernberg, Tomas (4); Hockings, Paul, 1956 (4); Hulthe, Johannes, 19 ... (4); Johansson, Lars (3); Abdellah, Tebani (3); Dodig-Crnkovic, Tea (3); Angerås, Oskar, 1976 (3); Ahlström, Håkan, 195 ... (3); Lind, Lars (3); Persson, Margaretha (3); Sundström, Johan, Pr ... (3); Nordmark, Eva (3); Söderberg, Stefan (3); Hong, Mun-Gwan (3); Hulthe, Johannes (3); Niessen, Heiko G (3); Schoelch, Corinna (3); Vessby, Johan (3); visa färre...

Lärosäte: Göteborgs universitet (44); Karolinska Institutet (16); Kungliga Tekniska Högskolan (13); Uppsala universitet (13); Lunds universitet (12); Chalmers tekniska högskola (10); visa fler...; Linköpings universitet (8); Umeå universitet (7); Luleå tekniska universitet (1); Örebro universitet (1); Malmö universitet (1); Gymnastik- och idrottshögskolan (1); Högskolan Dalarna (1); Sveriges Lantbruksuniversitet (1); visa färre...

Språk: Engelska (57); Svenska (3)

Forskningsämne (UKÄ/SCB): Medicin och hälsovetenskap (47); Naturvetenskap (6); Samhällsvetenskap (2); Teknik (1)

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