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1.
  • Alsharari, Zayed, et al. (författare)
  • Association between carbohydrate intake and fatty acids in the de novo lipogenic pathwayin serum phospholipids and adipose tissue among 63-year old men
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • AbstractBackground: Fatty acid composition in blood and adipose tissue is useful to reflect dietary fatquality, although the utility of even-chain saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) has been debated. Since SFA also can be produced via de novo lipogenesis (DNL), and desaturated to MUFA, it has been proposed that these fatty acids may reflect carbohydrate-induced DNL. We aimed to test the hypothesis that high carbohydrate intake, especially sugars, is related to SFA and MUFA in serum and adipose tissue.Methods: Validated 7-day food records were collected and fatty acid composition in serum phospholipids (PL) and adipose tissue (AT) were measured in 63-year-old men (n=299). Stearoyl-CoA desaturate (SCD) activities in AT and PL were estimated by the palmitoleic acid (16:1) to palmitic acid (16:0) ratio. Associations of dietary carbohydrate, disaccharides,  monosaccharides, carbohydrate-to-fiber ratio, and alcohol with the sum of even-chain SFA, 16:0, 16:1, and SCD activity were assessed using linear regression models with and without adjustment for BMI. Non-linear trends were evaluated using restricted cubic splines. In a subsample (n=81) with RNA measured in AT biopsies, associations of dietary carbohydrate and alcohol with SCD gene expression were assessed using linear regression models.Results: In BMI-adjusted models, intake of carbohydrates was inversely associated with palmitic acid in PL (P=0.005). Disaccharide intake was non-linearly associated with 16:1 and SCD activity in PL (P for nonlinear trend ≤0.02), with the lowest values observed in the mid tertile. Alcohol intake was linearly associated with 16:0 in PL (P<0.001) and with 16:1 (P<0.001) and SCD activity (P ≤0.005) in AT. Alcohol intake was non-linear associated (P≤0.02) with 16:1 and SCD activity in PL; with initially stable levels at lower intakes that rapidly increased at intakes above median. In the subsample, we found no associations between carbohydrate intake and SCD gene expression (P ≥0.08).Conclusion: In this Swedish population, we found no evidence to suggest that higher carbohydrate intake or sugar-rich foods or beverages is reflected by higher SFA in PL and AT.Instead, alcohol was consistently associated with higher SFA and MUFA.
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2.
  • Alsharari, Zayed, et al. (författare)
  • CarbohydrateIntake and Abdominal Obesity in Swedish Men
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • ABSTRACTBackground/Objectives: Associations between carbohydrates, particularly simple sugar and starch, and abdominal anthropometric measures appears controversial. However, the role of dietary carbohydrate intake in obesity and abdominal obesity has been debated, and few studies have been conducted in Nordic populations. We aim to examine the associations between carbohydrate quantity and quality, and anthropometric measures in Swedish men.Subjects/Methods: A cross-sectional investigation of 301 63-year-old men was conducted. Six men were excluded due to missing data on dietary intake and anthropometric measures, leaving 295 men for the present study. Healthy men were recruited from the Swedish 60YO cohort of men and women who had a health screening between 1997 to 1999. Carbohydrate and alcohol intake were assessed by a 7-days food record. The examination included anthropometric measurements (e. g., weight, BMI, WC, WHR, and SAD), fasting blood samples, and a comprehensive questionnaire. Spearman rank correlation and linear regression models were performed to assess relations between dietary intakes and anthropometric measures. Intakes of macronutrients were energy-adjusted according to the residual method. Logistic regression models were used to calculate odds ratios (OR) and 95% CI for abdominal obesity per intake tertiles.Results: Intakes of carbohydrate, monosaccharide, fibers, and fruits and vegetables correlated negatively with anthropometric measures of overall obesity (BMI) and AO (WC, WHR, and SAD). Total carbohydrate intake was significantly inversely associated with WHR and SAD. Likewise, monosaccharide intake was significantly associated with lower BMI, WC, WHR, and SAD. In contrast, alcohol intake was significantly associated with weight, BMI, WC, and SAD (Table 4). Alcohol intake was associated with AO (P for linear trend 0.002). Men in the highest tertile of alcohol intake were almost three times as likely to have AO compared to the men in the lowest tertile of intake, OR (95% CI): 2.93 (1.40-6.16). There was no evidence of non-linear association between the macronutrients and AO.Conclusion: In this Swedish population of older men, higher intakes of total carbohydrates and monosaccharides were associated a more favorable body fat distribution and lower abdominal adiposity. Men with higher alcohol intake were more likely to have AO as compared with a lower intake.
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3.
  • Alsharari, Zayed, et al. (författare)
  • Comparison of a 21-item food questionnaire with a 7-day dietary registration andbiomarkers of fat intake in a Swedish cohort of 60-year-old adults.
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • AbstractPurpose. To evaluate a 21-item food frequency questionnaire (FFQ) in men participating in alarge cohort of Swedish 60-year-old adults (60YO).Methods. A self-reported FFQ (including 21 qualitative and semi-quantitative questions) was completed by >2000 men as part of a detailed baseline examination. A subsample of 301 men was included in a subsequent study in which detailed dietary habits were determined by a 7-day food record. Spearman rank correlations (r) and weighted Kappa (Kw) statistics were used to compare food intake categories in FFQ and 7-day food record. Furthermore, fatty acid (FA) composition in serum cholesteryl esters, assessed concurrent with the FFQ completion, was used to evaluate intakes of specific fat-rich foods from the FFQ.Results. We found good agreement between FFQ and food records for the reported intake ofalcohol (r=0.72, Kw=0.51), margarine (r=0.60, Kw=0.33), and fruit (r=0.49, Kw=0.31), reasonably good agreement for total fish (r=0.25, Kw=0.23), and egg (r=0.35, Kw=0.28), but poor agreement for other food groups such as bread, cheese, vegetables and cookies. In addition, serum proportions of long-chain n-3 polyunsaturated FAs and pentadecanoic acid were significantly higher in men with greater intakes of fish and cheese, respectively.Conclusion. In this evaluation of a short FFQ against 7-d food records and serum biomarkers of fat intake we found that the FFQ reasonably well reflected the intake of certain food groups (e.g. alcohol, fish, and margarine), but performed less accurate for other food groups. Firm and overallconclusions on validity are confined by the time-lag between the test and the reference method.
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4.
  • Beretta, Chiara, et al. (författare)
  • Astrocytes with Alzheimer’s disease pathology provoke lipid droplet mediated cell-to-cell propagation of MHC II complexes
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Background. Astrocytes are critical for maintaining brain homeostasis, but are also highly involved in neuroinflammation. In the Alzheimer disease (AD) brain, reactive, inflammatory astrocytes are situated closely around amyloid β (Aβ) plaques. We have previously shown that reactive astrocytes ingest large quantities of soluble Aβ aggregates, but are unable to degrade the material, which leads to intracellular Aβ accumulation and severe cellular stress. A common response to cellular stress is the formation of lipid droplets (LDs). Novel data indicate that LDs play an important role in inflammatory processes. However, the involvement of LDs in AD inflammation and progression remains unclear.Methods. The aim of this study was to investigate how astrocytic Aβ pathology affects lipid metabolism and antigen presentation. For this purpose, human induced pluripotent stem cell (iPSC) derived astrocytes were exposed to soluble Aβ42 aggregates and analyzed over time, using a battery of experimental approaches.Results. Our results show that Aβ exposure induces LD accumulation in astrocytes, although the overall lipid composition remains unchanged. Moreover, astrocytes transfer LDs to neighboring cells via tunneling nanotubes (TNTs) and extracellular vesicle (EVs). Interestingly, we found that the antigen presenting protein major histocompatibility complex II (MHCII) is present inside LDs, suggesting an active role of LDs in astrocytic antigen presentation. Immunohistochemical analysis of human brain tissue verified the presence of LD-loaded MHCII+ astrocytes in AD individuals. Moreover, we found infiltrated CD4+ T cells to be in close contact with astrocytes, confirming an astrocyte T cell cross-talk in the AD brainConclusions. Taken together, our data show that Aβ pathology drastically affects lipid storage in astrocytes, which in turn modulates the astrocytic antigen presentation, indicating a role for astrocytic LDs in T cell responses in the AD brain.
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6.
  • Blomquist, Caroline, 1966-, et al. (författare)
  • Long-term effects of a Paleolithic diet on plasma fatty acid composition in postmenopausal women with obesity : a randomized trial
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Background: A Paleolithic-type diet (PD) can improve cardiometabolic risk factors, but its impact on plasma fatty acid (FA) composition is unknown. We hypothesized that a PD improves dietary fat quality and FA metabolism, which may help counteract obesity-related metabolic dysfunction. Objective: The current study investigated the impact of a PD on biomarkers of dietary fat quality and indices of FA desaturation and de novo lipogenesis compared with a prudent control diet (CD).Design: This randomized 2-year trial included 70 women (mean ± SD age 60 ± 5.6 years, BMI 33 ± 3.4). The PD was rich in fish and vegetable fats but devoid of dairy products and lower in carbohydrates than the CD advised to follow the Nordic Nutrition recommendations. FA composition of plasma cholesterol esters (CE) was assessed using gas chromatography, desaturase activities estimated by product-to-precursor FA ratios, and dietary intake measured by 4-day food records at baseline and after 6 and 24 months.Results: Saturated fat (P=0.009) and carbohydrate (P<0.001) intake was lower, whereas polyunsaturated (PUFA), monounsaturated FA, and protein intake were higher at 24 after PD versus CD (all P<0.001). Changes in plasma FA composition during PD compared to CD suggested that saturated FAs from dairy foods were partly replaced with PUFAs from fish and vegetable sources. Although comparable BMI, energy intake, and physical activity were found at 24 months with both diets, metabolic markers and desaturase activity indices, including 16:0 (P=0.005), 16:1n-7 (P=0.002), 20:3n-6 (P=0.004), stearoyl-CoA desaturase 1 (SCD-1) (P=0.006), lipogenic index (P<0.001), and the triglyceride/high-density lipoprotein cholesterol ratio (P=0.031), were lower after 24 months of PD versus CD.Conclusions: The PD had long-term effects on dietary fat quality intake and plasma FA composition, changes previously linked to improved cardiometabolic health. The results may suggest an anti-lipogenic effect of PD, possibly contributing to improved dyslipidemia.
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7.
  • Cedernaes, Jonathan, et al. (författare)
  • Fatty acid desaturase indices in rats : Associations between plasma, liver and adipose tissue lipid fractions and the effects of a high-fat diet and diet-induced obesity
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Alterations in fatty acid (FA) desaturase indices are linked to obesity-related disorders. As desaturases affect FA composition increased understanding of their regulation across lipid fractions with varying functions is essential. In this study we have examined desaturases and selected FAs to establish their degree of co-regulation in five different lipid fractions and under different dietary conditions, including diet-induced obesity (DIO).Methods: Sprague-Dawley rats were randomly grouped into three groups, one fed a chow diet ad libitum (control) and two fed a high-fat diet (HFD): one ad libitum (AL-HFD) and the other one calorically pair fed to the chow-fed group (HFD-paired). FA composition in subcutaneous adipose tissue triacylglycerols (SAT-TG), liver (phospholipids and triacylglycerols) and plasma (phospholipids and cholesterol esters) was assessed. Delta-5 desaturase (D5D), delta-6 desaturase (D6D) and stearoyl-CoA-desaturase 1 (SCD-16) indices were calculated from product-to-precursor FA ratios and proportions of long-chain FAs were measured.Results: Positive correlations were found for the desaturase indices between the five lipid fractions, especially for SCD-16 and almost exclusively between liver and plasma fractions. Only SCD-16 in SAT-TG of the AL-HFD group correlated with gain in body weight. Independent of weight gain, the HFD decreased all SCD-16 indices and most FA proportions, but D5D and D6D indices were fraction- and tissue-dependently increased.Conclusion: Desaturase indices are especially correlated for SCD-16 and between lipid and plasma lipid fractions, suggesting that SAT-TG desaturation is differentially regulated compared with the other studied lipid fractions. The correlations are however influenced by diet and weight gain, further suggesting such factors should be taken into account when using desaturase indices.
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8.
  • Diamanti, Klev, 1987-, et al. (författare)
  • Integration of whole-body PET/MRI with non-targeted metabolomics provides new insights into insulin sensitivity of various tissues
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Alteration of various metabolites has been linked to type 2 diabetes (T2D) and insulin resistance. However, identifying significant associations between metabolites and tissue-specific alterations is challenging and requires a multi-omics approach. In this study, we aimed at discovering associations of metabolites from subcutaneous adipose tissue (SAT) and plasma with the volume, the fat fraction (FF) and the insulin sensitivity (Ki) of specific tissues using [18F]FDG PET/MRI.Materials and Methods: In a cohort of 42 subjects with different levels of glucose tolerance (normal, prediabetes and T2D) matched for age and body-mass-index (BMI) we calculated associations between parameters of whole-body FDG PET/MRI during clamp and non-targeted metabolomics profiling for SAT and blood plasma. We also used a rule-based classifier to identify a large collection of prevalent patterns of co-dependent metabolites that characterize non-diabetes (ND) and T2D.Results: The plasma metabolomics profiling revealed that hepatic fat content was positively associated with tyrosine, and negatively associated with lysoPC(P-16:0). Ki in visceral adipose tissue (VAT) and SAT, was positively associated with several species of lysophospholipids while the opposite applied to branched-chain amino acids (BCAA) and their intermediates. The adipose tissue metabolomics revealed a positive association between non-esterified fatty acids and, VAT and liver Ki. On the contrary, bile acids and carnitines in adipose tissue were inversely associated with VAT Ki. Finally, we presented a transparent machine-learning model that predicted ND or T2D in “unseen” data with an accuracy of 78%.Conclusions: Novel associations of several metabolites from SAT and plasma with the FF, volume and insulin senstivity of various tissues throughout the body were discovered using PET/MRI and a new integrative multi-omics approach. A promising computational model that predicted ND and T2D with high certainty, suggested novel non-linear interdependencies of metabolites.
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9.
  • Fridén, Michael, et al. (författare)
  • Effects of a low-carbohydrate high polyunsaturated fat diet or a healthy Nordic diet versus usual care on liver fat content and cardiometabolic risk factors in people with type 2 diabetes and prediabetes: a randomized controlled trial (NAFLDiet)
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Previous trials have shown that plant-derived polyunsaturated fatty acids (PUFA) in place of saturated fat reduces liver fat, a prerequisite for non-alcoholic fatty liver disease (NAFLD). The effect on liver fat from a novel “anti-lipogenic diet” replacing carbohydrates with PUFA or a healthy Nordic diet (HND) higher in whole-grains but lower in saturated fat has not yet been examined. Objectives: To investigate the effects on changes in liver fat (primary outcome) and other cardiometabolic risk factors after 12 months of follow-up in individuals with prediabetes or T2D from three different diet comparisons: a low carbohydrate high PUFA (LCPUFA) diet versus a HND, a LCPUFA diet versus usual care (UC) and a HND versus UC. Methods: A three-arm parallel ad libitum randomized trial was conducted. Adult men and women (n=148) were randomized to one of the three diet groups. Participants in all groups received key food items on a monthly/bimonthly basis. Liver fat and cardiometabolic risk factors were assessed at baseline and after 12 months. Dietary adherence was assessed using weighed food diaries and objective biomarkers. General linear models were employed to estimate the intention-to-treat (ITT) effect. Results: Dietary adherence was high for all diet groups. Liver fat was reduced to a similar extent in the LCPUFA and the HND group compared to UC (-1.46% (95% CI: -2.42, -0.51)) and -1.76 % (95% CI: -2.96, -0.57), respectively. No difference in liver fat between LCPUFA and HND was observed. Body weight and HbA1c decreased more in the HND compared to the other diet groups whereas no differences were observed between LCPUFA and UC. Similar reductions in LDL-cholesterol were observed for the HND and the LCPUFA group compared to UC, but only the HND reduced triglycerides and C-reactive protein (CRP) compared with UC. No differences were observed for any other secondary outcomes.Conclusions: A LCPUFA diet and a HND both reduced liver fat as compared with UC. Given the sustained weight loss after the HND compared to the other groups, together with improvements in other cardiometabolic markers, the HND in particular seems to be useful for the treatment of T2D and NAFLD.
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10.
  • Iggman, David, 1981-, et al. (författare)
  • Adipose tissue fatty acids and cardiovascular and all-cause mortality in elderly men : a prospective cohort study
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Background: For several fatty acids, adipose tissue reflects long-term dietary intake and may provide more objective information than self-reported intake. No prospective studies have examined whether adipose tissue fatty acids predict cardiovascular and all-cause mortality.Objective: To investigate associations between adipose tissue fatty acids and cardiovascular and overall mortality in a cohort of elderly men. We hypothesized that polyunsaturated fatty acids (PUFA) could be inversely associated with cardiovascular and all-cause mortality.Methods: In the Swedish community-based cohort study ULSAM, adipose tissue biopsies were taken from the buttocks of 853 men at age 71. Cox regression analyses were performed primarily for four PUFA that were considered to reflect dietary intake (linoleic acid, 18:2n-6, alpha-linolenic acid, 18:3n-3, eicosapentaenoic acid, 20:5n-3, and docosahexaenoic acid, 22:6n-3), and for all other available fatty acids (secondary analyses) analyzed by gas-liquid chromatography.Results: During 20-year follow-up, 605 individuals died of which 251 were cardiovascular deaths. After adjusting for risk factors, none of the four primary fatty acids were associated with cardiovascular mortality (hazard ratios (HR)=0.92-1.05 for each SD increase, P≥0.27). Linoleic acid was inversely associated with mortality (HR=0.90, 95% confidence interval (CI) 0.82-0.99, P=0.03). In secondary analyses, palmitoleic acid, 16:1n-7, (HR=1.11, 95% CI 1.02-1.21, P=0.01), and arachidonic acid, 20:4n-6, (HR=1.09, 95% CI 1.00-1.19, P=0.05) were associated with increased mortality, whereas heptadecanoic acid, 17:0, was inversely associated with mortality (HR=0.89, 95% CI 0.79-1.00, P=0.05).Conclusions: Adipose tissue PUFA was inversely associated with total mortality, but not cardiovascular mortality in elderly men. The mechanisms behind adipose tissue PUFA and longevity warrant further investigation.
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