| 291. |
- Rosqvist, Fredrik, 1985-, et al.
(författare)
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Abdominal Fat and Metabolic Health Markers but Not PNPLA3 Genotype Predicts Liver Fat Accumulation in Response to Excess Intake of Energy and Saturated Fat in Healthy Individuals
- 2020
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Ingår i: Frontiers in Nutrition. - : Frontiers Media SA. - 2296-861X. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Saturated fat (SFA) has consistently been shown to increase liver fat, but the response appears variable at the individual level. Phenotypic and genotypic characteristics have been demonstrated to modify the hypercholesterolemic effect of SFA but it is unclear which characteristics that predict liver fat accumulation in response to a hypercaloric diet high in SFA.Objective: To identify predictors of liver fat accumulation in response to an increased intake of SFA.Design: We pooled our two previously conducted double-blind randomized trials (LIPOGAIN and LIPOGAIN-2, clinicaltrials.gov NCT01427140 and NCT02211612) and used data from the n = 49 metabolically healthy men (n = 32) and women (n = 17) randomized to a hypercaloric diet through addition of SFA-rich muffins for 7-8 weeks. Associations between clinical and metabolic variables at baseline and changes in liver fat during the intervention were analyzed using Spearman rank correlation. Linear regression was used to generate a prediction model.Results: Liver fat increased by 33% (IQR 5.4-82.7%; P < 0.0001) in response to excess energy intake and this was not associated (r = 0.17, P = 0.23) with the increase in body weight (1.9 kg; IQR 1.1-2.9 kg). Liver fat accumulation was similar (P = 0.28) in carriers (33%, IQR 14-79%) and non-carriers (33%, IQR -11 to +87%) of the PNPLA3-I148M variant. Baseline visceral and liver fat content, as well as levels of the liver enzyme gamma-glutamyl transferase (GT), were the strongest positive predictors of liver fat accumulation-in contrast, adiponectin and the fatty acid 17:0 in adipose tissue were the only negative predictors in univariate analyses. A regression model based on eight clinical and metabolic variables could explain 81% of the variation in liver fat accumulation.Conclusion: Our results suggest there exists a highly inter-individual variation in the accumulation of liver fat in metabolically healthy men and women, in response to an increased energy intake from SFA and carbohydrates that occurs over circa 2 months. This marked variability in liver fat accumulation could largely be predicted by a set of clinical (e.g., GT and BMI) and metabolic (e.g., fatty acids, HOMA-IR, and adiponectin) variables assessed at baseline.
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| 292. |
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| 293. |
- Rosqvist, Fredrik, 1985-, et al.
(författare)
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Overeating saturated fat promotes fatty liver and ceramides compared to polyunsaturated fat : a randomized trial
- 2019
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 104:12, s. 6207-6219
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Saturated fat (SFA) versus polyunsaturated fat (PUFA) may promote non-alcoholic fatty liver disease (NAFLD) by yet unclear mechanisms.OBJECTIVE: To investigate if overeating SFA- and PUFA-enriched diets lead to differential liver fat accumulation in overweight and obese humans.DESIGN: Double-blind randomized trial (LIPOGAIN-2). Overfeeding SFA vs PUFA for 8 weeks, followed by 4 weeks of caloric restriction.SETTING: General community.Participants: n=61 overweight or obese men and women.INTERVENTION: Muffins high in either palm (SFA)- or sunflower oil (PUFA) were added to the habitual diet.MAIN OUTCOME MEASURE: Lean tissue mass (not reported here). Secondary and exploratory outcomes included liver and ectopic fat depots.RESULTS: By design, body weight gain was similar in SFA (2.31±1.38 kg) and PUFA (2.01±1.90 kg) groups, P=0.50. SFA markedly induced liver fat content (50% relative increase) along with liver enzymes and atherogenic serum lipids. In contrast, despite similar weight gain, PUFA did not increase liver fat or liver enzymes or cause any adverse effects on blood lipids. SFA had no differential effect on the accumulation of visceral fat, pancreas fat or total body fat compared with PUFA. SFA consistently increased, while PUFA reduced circulating ceramides; changes that were moderately associated with liver fat changes and proposed markers of hepatic lipogenesis. The adverse metabolic effects of SFA were reversed by calorie restriction.CONCLUSIONS: Saturated fat markedly induces liver fat and serum ceramides whereas dietary polyunsaturated fat prevent liver fat accumulation, reduce ceramides and hyperlipidemia during excess energy intake and weight gain in overweight individuals.
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| 294. |
- Rukh, Gull, et al.
(författare)
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Dietary starch intake modifies the relation between copy number variation in the salivary amylase gene and BMI
- 2017
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165. ; 106:1, s. 256-262
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies have shown conflicting associations between the salivary amylase gene (AMY1) copy number and obesity. Salivary amylase initiates starch digestion in the oral cavity; starch is a major source of energy in the diet. Objective: We investigated the association between AMY1 copy number and obesity traits, and the effect of the interaction between AMY1 copy number and starch intake on these obesity traits. Design: We first assessed the association between AMY1 copy number (genotyped by digital droplet polymerase chain reaction) and obesity traits in 4800 individuals without diabetes (mean age: 57 y; 60% female) from the Malmo "Diet and Cancer Cohort. Then we analyzed interactions between AMY1 copy number and energyadjusted starch intake (obtained by a modified diet history method) on body mass index (BMI) and body fat percentage. Results: AMY1 copy number was not associated with BMI (P = 0.80) or body fat percentage (P = 0.38). We observed a significant effect of the interaction between AMY1 copy number and starch intake on BMI (P-interaction = 0.007) and body fat percentage (P-interaction = 0.03). Upon stratification by dietary starch intake, BMI tended to decrease with increasing AMY1 copy numbers in the low-starch intake group (P = 0.07) and tended to increase with increasing AMY1 copy numbers in the high-starch intake group (P = 0.08). The lowest mean BMI was observed in the group of participants with a low AMY1 copy number and a high dietary intake of starch. Conclusions: Our findings suggest an effect of the interaction between starch intake and AMY1 copy number on obesity. Individuals with high starch intake but low genetic capacity to digest starch had the lowest BMI, potentially because larger amounts of undigested starch are transported through the gastrointestinal tract, contributing to fewer calories extracted from ingested starch.
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| 295. |
- Sammalisto, S, et al.
(författare)
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A male-specific quantitative trait locus on 1p21 controlling human stature
- 2005
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Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 42:12, s. 932-939
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Tidskriftsartikel (refereegranskat)abstract
- Background: Many genome-wide scans aimed at complex traits have been statistically underpowered due to small sample size. Combining data from several genome-wide screens with comparable quantitative phenotype data should improve statistical power for the localisation of genomic regions contributing to these traits. Objective: To perform a genome-wide screen for loci affecting adult stature by combined analysis of four previously performed genome-wide scans. Methods: We developed a web based computer tool, Cartographer, for combining genetic marker maps which positions genetic markers accurately using the July 2003 release of the human genome sequence and the deCODE genetic map. Using Cartographer, we combined the primary genotype data from four genome-wide scans and performed variance components (VC) linkage analyses for human stature on the pooled dataset of 1417 individuals from 277 families and performed VC analyses for males and females separately. Results: We found significant linkage to stature on 1p21 (multipoint LOD score 4.25) and suggestive linkages on 9p24 and 18q21 (multipoint LOD scores 2.57 and 2.39, respectively) in males-only analyses. We also found suggestive linkage to 4q35 and 22q13 (multipoint LOD scores 2.18 and 2.85, respectively) when we analysed both females and males and to 13q12 (multipoint LOD score 2.66) in females-only analyses. Conclusions: We strengthened the evidence for linkage to previously reported quantitative trait loci (QTL) for stature and also found significant evidence of a novel male-specific QTL on 1p21. Further investigation of several interesting candidate genes in this region will help towards characterisation of this first sex-specific locus affecting human stature.
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| 296. |
- Saxena, Richa, et al.
(författare)
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Common single nucleotide polymorphisms in TCF7L2 are reproducibly associated with type 2 diabetes and reduce the insulin response to glucose in nondiabetic individuals
- 2006
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 55:10, s. 2890-2895
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Tidskriftsartikel (refereegranskat)abstract
- Recently, common noncoding variants in the TCF7L2 gene were strongly associated with increased risk of type 2 diabetes in samples from Iceland, Denmark, and the U.S. We genotyped 13 single nucleotide polymorphisms (SNPs) across TCF7L2 in 8,310 individuals in family-based and case-control designs from Scandinavia, Poland, and the U.S. We convincingly confirmed the previous association of TCF7L2 SNPs with the risk of type 2 diabetes (rs7903146T odds ratio 1.40 [95% CI 1.30-1.50], P = 6.74 x 10(-20)). In nondiabetic individuals, the risk genotypes were associated with a substantial reduction in the insulinogenic index derived from an oral glucose tolerance test (risk allele homozygotes have half the insulin response to glucose of noncarriers, P = 0.003) but not with increased insulin resistance. These results suggest that TCF7L2 variants may act through insulin secretion to increase the risk of type 2 diabetes.
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| 297. |
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| 298. |
- Sayols-Baixeras, Sergi, et al.
(författare)
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Streptococcus Species Abundance in the Gut Is Linked to Subclinical Coronary Atherosclerosis in 8973 Participants From the SCAPIS Cohort
- 2023
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Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 148:6, s. 459-472
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gut microbiota have been implicated in atherosclerotic disease, but their relation with subclinical coronary atherosclerosis is unclear. This study aimed to identify associations between the gut microbiome and computed tomography-based measures of coronary atherosclerosis and to explore relevant clinical correlates.Methods: We conducted a cross-sectional study of 8973 participants (50 to 65 years of age) without overt atherosclerotic disease from the population-based SCAPIS (Swedish Cardiopulmonary Bioimage Study). Coronary atherosclerosis was measured using coronary artery calcium score and coronary computed tomography angiography. Gut microbiota species abundance and functional potential were assessed with shotgun metagenomics sequencing of stool, and associations with coronary atherosclerosis were evaluated with multivariable regression models adjusted for cardiovascular risk factors. Associated species were evaluated for association with inflammatory markers, metabolites, and corresponding species in saliva.Results: The mean age of the study sample was 57.4 years, and 53.7% were female. Coronary artery calcification was detected in 40.3%, and 5.4% had at least 1 stenosis with >50% occlusion. Sixty-four species were associated with coronary artery calcium score independent of cardiovascular risk factors, with the strongest associations observed for Streptococcus anginosus and Streptococcus oralis subsp oralis (P<1×10-5). Associations were largely similar across coronary computed tomography angiography-based measurements. Out of the 64 species, 19 species, including streptococci and other species commonly found in the oral cavity, were associated with high-sensitivity C-reactive protein plasma concentrations, and 16 with neutrophil counts. Gut microbial species that are commonly found in the oral cavity were negatively associated with plasma indole propionate and positively associated with plasma secondary bile acids and imidazole propionate. Five species, including 3 streptococci, correlated with the same species in saliva and were associated with worse dental health in the Malmö Offspring Dental Study. Microbial functional potential of dissimilatory nitrate reduction, anaerobic fatty acid β-oxidation, and amino acid degradation were associated with coronary artery calcium score.Conclusions: This study provides evidence of an association of a gut microbiota composition characterized by increased abundance of Streptococcus spp and other species commonly found in the oral cavity with coronary atherosclerosis and systemic inflammation markers. Further longitudinal and experimental studies are warranted to explore the potential implications of a bacterial component in atherogenesis.
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| 299. |
- Sayols-Baixeras, Sergi, et al.
(författare)
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Streptococcus Species Abundance in the Gut Is Linked to Subclinical Coronary Atherosclerosis in 8973 Participants From the SCAPIS Cohort
- 2023
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Ingår i: Circulation. - : American Heart Association. - 0009-7322 .- 1524-4539. ; 148:6, s. 459-472
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Gut microbiota have been implicated in atherosclerotic disease, but their relation with subclinical coronary atherosclerosis is unclear. This study aimed to identify associations between the gut microbiome and computed tomography–based measures of coronary atherosclerosis and to explore relevant clinical correlates.METHODS: We conducted a cross-sectional study of 8973 participants (50 to 65 years of age) without overt atherosclerotic disease from the population-based SCAPIS (Swedish Cardiopulmonary Bioimage Study). Coronary atherosclerosis was measured using coronary artery calcium score and coronary computed tomography angiography. Gut microbiota species abundance and functional potential were assessed with shotgun metagenomics sequencing of fecal samples, and associations with coronary atherosclerosis were evaluated with multivariable regression models adjusted for cardiovascular risk factors. Associated species were evaluated for association with inflammatory markers, metabolites, and corresponding species in saliva.RESULTS: The mean age of the study sample was 57.4 years, and 53.7% were female. Coronary artery calcification was detected in 40.3%, and 5.4% had at least 1 stenosis with >50% occlusion. Sixty-four species were associated with coronary artery calcium score independent of cardiovascular risk factors, with the strongest associations observed for Streptococcus anginosus and Streptococcus oralis subsp oralis (P<1×10–5). Associations were largely similar across coronary computed tomography angiography–based measurements. Out of the 64 species, 19 species, including streptococci and other species commonly found in the oral cavity, were associated with high-sensitivity C-reactive protein plasma concentrations, and 16 with neutrophil counts. Gut microbial species that are commonly found in the oral cavity were negatively associated with plasma indole propionate and positively associated with plasma secondary bile acids and imidazole propionate. Five species, including 3 streptococci, correlated with the same species in saliva and were associated with worse dental health in the Malmö Offspring Dental Study. Microbial functional potential of dissimilatory nitrate reduction, anaerobic fatty acid β-oxidation, and amino acid degradation were associated with coronary artery calcium score.CONCLUSIONS: This study provides evidence of an association of a gut microbiota composition characterized by increased abundance of Streptococcus spp and other species commonly found in the oral cavity with coronary atherosclerosis and systemic inflammation markers. Further longitudinal and experimental studies are warranted to explore the potential implications of a bacterial component in atherogenesis.
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| 300. |
- Sevastianova, Ksenia, et al.
(författare)
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Genetic variation in PNPLA3 (adiponutrin) confers sensitivity to weight loss-induced decrease in liver fat in humans
- 2011
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 1938-3207 .- 0002-9165. ; 94:1, s. 104-111
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Tidskriftsartikel (refereegranskat)abstract
- Background: The rs738409 C -> G single nucleotide polymorphism in the patatin-like phospholipase domain-containing 3 (PNPLA3; adiponutrin) leads to a missense mutation (I148M), which is associated with increased liver fat but not insulin resistance. The I148M mutation impedes triglyceride hydrolysis in vitro, and its carriers have an increased risk of developing severe liver disease. Objective: We explored whether the rs738409 PNPLA3 G allele influences the ability of weight loss to decrease liver fat or change insulin sensitivity. Design: We recruited 8 subjects who were homozygous for the rs738409 PNPLA3 G allele (PNPLA3-148MM) and 10 who were homozygous for the rs738409 PNPLA3 C allele (PNPLA3-148II). To allow comparison of changes in liver fat, the groups were matched with respect to baseline age, sex, body mass index, and liver fat. The subjects were placed on a hypocaloric low-carbohydrate diet for 6 d. Liver fat content (proton magnetic resonance spectroscopy), whole-body insulin sensitivity of glucose metabolism (euglycemic clamp technique), and lipolysis ([H-2(5)] glycerol infusion) were measured before and after the diet. Results: At baseline, fasting serum insulin and C-peptide concentrations were significantly lower in the PNPLA3-148MM group than in the PNPLA3-148II group, as predicted by study design. Weight loss was not significantly different between groups (PNPLA3-148MM: -3.1 +/- 0.5 kg; PNPLA3-148II: -3.1 +/- 0.4 kg). Liver fat decreased by 45% in the PNPLA3-148MM group (P < 0.001) and by 18% in the PNPLA3-148II group (P < 0.01). Conclusion: Weight loss is effective in decreasing liver fat in subjects who are homozygous for the rs738409 PNPLA3 G or C allele. This trial was registered at www.hus.fi as 233775. Am J Clin Nutr 2011;94:104-11.
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