| 11. |
- Perez-Martinez, Pablo, et al.
(författare)
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Gene-nutrient interactions on the phosphoenolpyruvate carboxykinase influence insulin sensitivity in metabolic syndrome subjects
- 2013
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Ingår i: Clinical Nutrition. - : Elsevier BV. - 0261-5614 .- 1532-1983. ; 32:4, s. 630-635
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Tidskriftsartikel (refereegranskat)abstract
- Background & aims: Genetic background may interact with habitual dietary fat composition, and affect development of the metabolic syndrome (MetS). The phosphoenolpyruvate carboxykinase gene (PCK1) plays a significant role regulating glucose metabolism, and fatty acids are key metabolic regulators, which interact with transcription factors and influence glucose metabolism. We explored genetic variability at the PCK1 gene locus in relation to degree of insulin resistance and plasma fatty acid levels in MetS subjects. Moreover, we analyzed the PCK1 gene expression in the adipose tissue of a subgroup of MetS subjects according to the PCK1 genetic variants. Methods: Insulin sensitivity, insulin secretion, glucose effectiveness, plasma concentrations of C-peptide, fatty acid composition and three PCK1 tag-single nucleotide polymorphisms (SNPs) were determined in 443 MetS participants in the UPGENE cohort. Results: The rs2179706 SNP interacted with plasma concentration of n - 3 polyunsaturated fatty acids (n - 3 PUFA), which were significantly associated with plasma concentrations of fasting insulin, peptide C, and HOMA-IR. Among subjects with n - 3 PUFA levels above the population median, carriers of the C/C genotype exhibited lower plasma concentrations of fasting insulin (P = 0.036) and HOMA-IR (P = 0.019) as compared with C/C carriers with n - 3 PUFA below the median. Moreover, homozygous C/C subjects with n - 3 PUFA levels above the median showed lower plasma concentrations of peptide C as compared to individuals with the T-allele (P = 0.006). Subjects carrying the T-allele showed a lower gene PCK1 expression as compared with carriers of the C/C genotype (P = 0.015). Conclusions: The PCK1 rs2179706 polymorphism interacts with plasma concentration of n - 3 PUFA levels modulating insulin resistance in MetS subjects.
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| 12. |
- Perez-Martinez, Pablo, et al.
(författare)
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Glucokinase Regulatory Protein Genetic Variant Interacts with Omega-3 PUFA to Influence Insulin Resistance and Inflammation in Metabolic Syndrome
- 2011
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:6, s. e20555-
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Tidskriftsartikel (refereegranskat)abstract
- Glucokinase Regulatory Protein (GCKR) plays a central role regulating both hepatic triglyceride and glucose metabolism. Fatty acids are key metabolic regulators, which interact with genetic factors and influence glucose metabolism and other metabolic traits. Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been of considerable interest, due to their potential to reduce metabolic syndrome (MetS) risk. Objective: To examine whether genetic variability at the GCKR gene locus was associated with the degree of insulin resistance, plasma concentrations of C-reactive protein (CRP) and n-3 PUFA in MetS subjects. Design: Homeostasis model assessment of insulin resistance (HOMA-IR), HOMA-B, plasma concentrations of C-peptide, CRP, fatty acid composition and the GCKR rs1260326-P446L polymorphism, were determined in a cross-sectional analysis of 379 subjects with MetS participating in the LIPGENE dietary cohort. Results: Among subjects with n-3 PUFA levels below the population median, carriers of the common C/C genotype had higher plasma concentrations of fasting insulin (P = 0.019), C-peptide (P = 0.004), HOMA-IR (P = 0.008) and CRP (P = 0.032) as compared with subjects carrying the minor T-allele (Leu446). In contrast, homozygous C/C carriers with n-3 PUFA levels above the median showed lower plasma concentrations of fasting insulin, peptide C, HOMA-IR and CRP, as compared with individuals with the T-allele. Conclusions: We have demonstrated a significant interaction between the GCKR rs1260326-P446L polymorphism and plasma n-3 PUFA levels modulating insulin resistance and inflammatory markers in MetS subjects. Further studies are needed to confirm this gene-diet interaction in the general population and whether targeted dietary recommendations can prevent MetS in genetically susceptible individuals.
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| 13. |
- Perez-Martinez, Pablo, et al.
(författare)
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Insulin receptor substrate-2 gene variants in subjects with metabolic syndrome : Association with plasma monounsaturated and n-3 polyunsaturated fatty acid levels and insulin resistance
- 2012
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Ingår i: Molecular Nutrition & Food Research. - : Wiley. - 1613-4125 .- 1613-4133. ; 56:2, s. 309-315
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Tidskriftsartikel (refereegranskat)abstract
- Scope: Several insulin receptor substrate-2 (IRS-2) polymorphisms have been studied in relation to insulin resistance and type 2 diabetes. To examine whether the genetic variability at the IRS-2 gene locus was associated with the degree of insulin resistance and plasma fatty acid levels in metabolic syndrome (MetS) subjects.Methods and results: Insulin sensitivity, insulin secretion, glucose effectiveness, plasma fatty acid composition and three IRS-2 tag-single nucleotide polymorphisms (SNPs) were determined in 452 MetS subjects. Among subjects with the lowest level of monounsaturated (MUFA) (below the median), the rs2289046 A/A genotype was associated with lower glucose effectiveness (p < 0.038), higher fasting insulin concentrations (p < 0.028) and higher HOMA IR (p < 0.038) as compared to subjects carrying the minor G-allele (A/G and G/G). In contrast, among subjects with the highest level of MUFA (above the median), the A/A genotype was associated with lower fasting insulin concentrations and HOMA-IR, whereas individuals carrying the G allele and with the highest level of omega-3 polyunsaturated fatty acids (above the median) showed lower fasting insulin (p < 0.01) and HOMA-IR (p < 0.02) as compared with A/A subjects.Conclusion: The rs2289046 polymorphism at the IRS2 gene locus may influence insulin sensitivity by interacting with certain plasma fatty acids in MetS subjects.
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| 14. |
- Phillips, Catherine M., et al.
(författare)
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ACC2 gene polymorphisms, metabolic syndrome, and gene-nutrient interactions with dietary fat
- 2010
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Ingår i: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 51:12, s. 3500-3507
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Tidskriftsartikel (refereegranskat)abstract
- Acetyl-CoA carboxylase beta (ACC2) plays a key role in fatty acid synthesis and oxidation pathways. Disturbance of these pathways is associated with impaired insulin responsiveness and metabolic syndrome (MetS). Gene-nutrient interactions may affect MetS risk. This study determined the relationship between ACC2 polymorphisms (rs2075263, rs2268387, rs2284685, rs2284689, rs2300453, rs3742023, rs3742026, rs4766587, and rs6606697) and MetS risk, and whether dietary fatty acids modulate this in the LIPGENE-SU. VI.MAX study of MetS cases and matched controls (n = 1754). Minor A allele carriers of rs4766587 had increased MetS risk (OR 1.29 [CI 1.08, 1.58], P = 0.0064) compared with the GG homozygotes, which may in part be explained by their increased body mass index (BMI), abdominal obesity, and impaired insulin sensitivity (P < 0.05). MetS risk was modulated by dietary fat intake (P = 0.04 for gene-nutrient interaction), where risk conferred by the A allele was exacerbated among individuals with a high-fat intake (>35% energy) (OR 1.62 [CI 1.05, 2.50], P = 0.027), particularly a high intake (>5.5% energy) of n-6 polyunsaturated fat (PUFA) (OR 1.82 [CI 1.14, 2.94], P = 0.01; P = 0.05 for gene-nutrient interaction). Saturated and monounsaturated fat intake did not modulate MetS risk. Importantly, we replicated some of these findings in an independent cohort.jlr In conclusion, the ACC2 rs4766587 polymorphism influences MetS risk, which was modulated by dietary fat, suggesting novel gene-nutrient interactions.-Phillips, C. M., L. Goumidi, S. Bertrais, M. R. Field, L. Adrienne Cupples, J. M. Ordovas, J. McMonagle, C. Defoort, J. A. Lovegrove, C. A. Drevon, E. E. Blaak, B. Kiec-Wilk, U. Riserus, J. Lopez-Miranda, R. McManus, S. Hercberg, D. Lairon, R. Planells, and H. M. Roche. ACC2 gene polymorphisms, metabolic syndrome, and gene-nutrient interactions with dietary fat.
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| 15. |
- Phillips, Catherine M, et al.
(författare)
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Gene-nutrient interactions with dietary fat modulate the association between genetic variation of the ACSL1 gene and metabolic syndrome
- 2010
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Ingår i: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 51:7, s. 1793-1800
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Tidskriftsartikel (refereegranskat)abstract
- Long-chain acyl CoA synthetase 1 (ACSL1) plays an important role in fatty acid metabolism and triacylglycerol (TAG) synthesis. Disturbance of these pathways may result in dyslipidemia and insulin resistance, hallmarks of the metabolic syndrome (MetS). Dietary fat is a key environmental factor that may interact with genetic determinants of lipid metabolism to affect MetS risk. We investigated the relationship between ACSL1 polymorphisms (rs4862417, rs6552828, rs13120078, rs9997745, and rs12503643) and MetS risk and determined potential interactions with dietary fat in the LIPGENE-SU.VI.MAX study of MetS cases and matched controls (n = 1,754). GG homozygotes for rs9997745 had increased MetS risk {odds ratio (OR) 1.90 [confidence interval (CI) 1.15, 3.13]; P = 0.01}, displayed elevated fasting glucose (P = 0.001) and insulin concentrations (P = 0.002) and increased insulin resistance (P = 0.03) relative to the A allele carriers. MetS risk was modulated by dietary fat, whereby the risk conferred by GG homozygosity was abolished among individuals consuming either a low-fat (<35% energy) or a high-PUFA diet (>5.5% energy). In conclusion, ACSL1 rs9997745 influences MetS risk, most likely via disturbances in fatty acid metabolism, which was modulated by dietary fat consumption, particularly PUFA intake, suggesting novel gene-nutrient interactions.
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| 16. |
- Phillips, Catherine M, et al.
(författare)
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Leptin receptor polymorphisms interact with polyunsaturated fatty acids to augment risk of insulin resistance and metabolic syndrome in adults
- 2010
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Ingår i: Journal of Nutrition. - : Elsevier BV. - 0022-3166 .- 1541-6100. ; 140:2, s. 238-244
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Tidskriftsartikel (refereegranskat)abstract
- The leptin receptor (LEPR) is associated with insulin resistance, a key feature of metabolic syndrome (MetS). Gene-fatty acid interactions may affect MetS risk. The objective was to investigate the relationship among LEPR polymorphisms, insulin resistance, and MetS risk and whether plasma fatty acids, a biomarker of dietary fatty acids, modulate this. LEPR polymorphisms (rs10493380, rs1137100, rs1137101, rs12067936, rs1805096, rs2025805, rs3790419, rs3790433, rs6673324, and rs8179183), biochemical measurements, and plasma fatty acid profiles were determined in the LIPGENE-SU.VI.MAX study of MetS cases and matched controls (n = 1754). LEPR rs3790433 GG homozygotes had increased MetS risk compared with the minor A allele carriers [odds ratio (OR) = 1.65; 95% CI: 1.05-2.57; P = 0.028], which may be accounted for by their increased risk of elevated insulin concentrations (OR 2.40; 95% CI: 1.28-4.50; P = 0.006) and insulin resistance (OR = 2.15; 95% CI: 1.18-3.90; P = 0.012). Low (less than median) plasma (n-3) and high (n-6) PUFA status exacerbated the genetic risk conferred by GG homozygosity to hyperinsulinemia (OR 2.92-2.94) and insulin resistance (OR 3.40-3.47). Interestingly, these associations were abolished against a high (n-3) or low (n-6) PUFA background. Importantly, we replicated some of these findings in an independent cohort. Homozygosity for the LEPR rs3790433 G allele was associated with insulin resistance, which may predispose to increased MetS risk. Novel gene-nutrient interactions between LEPR rs3790433 and PUFA suggest that these genetic influences were more evident in individuals with low plasma (n-3) or high plasma (n-6) PUFA.
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| 17. |
- Phillips, Catherine M., et al.
(författare)
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Obesity and Body Fat Classification in the Metabolic Syndrome : Impact on Cardiometabolic Risk Metabotype
- 2013
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Ingår i: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 21:1, s. E154-E161
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Obesity is a key factor in the development of the metabolic syndrome (MetS), which is associated with increased cardiometabolic risk. We investigated whether obesity classification by BMI and body fat percentage (BF%) influences cardiometabolic profile and dietary responsiveness in 486 MetS subjects (LIPGENE dietary intervention study). Design and Methods: Anthropometric measures, markers of inflammation and glucose metabolism, lipid profiles, adhesion molecules, and hemostatic factors were determined at baseline and after 12 weeks of four dietary interventions (high saturated fat (SFA), high monounsaturated fat (MUFA), and two low fat high complex carbohydrate (LFHCC) diets, one supplemented with long chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs)). Results: About 39 and 87% of subjects classified as normal and overweight by BMI were obese according to their BF%. Individuals classified as obese by BMI (>= 30 kg/m(2)) and BF% (>= 25% (men) and >= 35% (women)) (OO, n = 284) had larger waist and hip measurements, higher BMI and were heavier (P < 0.001) than those classified as nonobese by BMI but obese by BF% (NOO, n = 92). OO individuals displayed a more proinflammatory (higher C reactive protein (CRP) and leptin), prothrombotic (higher plasminogen activator inhibitor-1 (PAI-1)), proatherogenic (higher leptin/adiponectin ratio) and more insulin resistant (higher HOMA-IR) metabolic profile relative to the NOO group (P < 0.001). Interestingly, tumor necrosis factor-alpha (TNF-alpha) concentrations were lower post-intervention in NOO individuals compared with OO subjects (P < 0.001). Conclusions: In conclusion, assessing BF% and BMI as part of a metabotype may help to identify individuals at greater cardiometabolic risk than BMI alone.
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| 18. |
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| 19. |
- Gulseth, Hanne L., et al.
(författare)
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Dietary fat modifications and blood pressure in subjects with the metabolic syndrome in the LIPGENE dietary intervention study
- 2010
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Ingår i: British Journal of Nutrition. - 0007-1145 .- 1475-2662. ; 104:2, s. 160-163
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Tidskriftsartikel (refereegranskat)abstract
- Hypertension is a key feature of the metabolic syndrome. Lifestyle and dietary changes may affect blood pressure (BP), but the knowledge of the effects of dietary fat modification in subjects with the metabolic syndrome is limited. The objective of the present study was to investigate the effect of an isoenergetic change in the quantity and quality of dietary fat on BP in subjects with the metabolic syndrome. In a 12-week European multi-centre, parallel, randomised controlled dietary intervention trial (LIPGENE), 486 subjects were assigned to one of the four diets distinct in fat quantity and quality: two high-fat diets rich in saturated fat or monounsaturated fat and two low-fat, high-complex carbohydrate diets with or without 1.2 g/d of very long-chain n-3 PUFA supplementation. There were no overall differences in systolic BP (SBP), diastolic BP or pulse pressure (PP) between the dietary groups after the intervention. The high-fat diet rich in saturated fat had minor unfavourable effects on SBP and PP in males.
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| 20. |
- Jans, Anneke, et al.
(författare)
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Transcriptional Metabolic Inflexibility in Skeletal Muscle Among Individuals With Increasing Insulin Resistance
- 2011
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Ingår i: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 19:11, s. 2158-2166
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Tidskriftsartikel (refereegranskat)abstract
- Disturbances in skeletal muscle lipid metabolism may play an important role in development of insulin resistance (IR). The aim was to investigate transcriptional control of skeletal muscle fatty acid (FA) metabolism in individuals with the metabolic syndrome (MetS) with varying degrees of insulin sensitivity (S(I)). 122 individuals with MetS (NCEP-ATP III criteria) at age 35-70 years, BMI 27-38 kg/m(2) were studied (subgroup EU-LIPGENE study). Individuals were divided into quartiles of S(I) measured during a frequently sampled insulin modified intravenous glucose tolerance test. Skeletal muscle normalized mRNA expression levels of genes important in skeletal muscle FA handling were analyzed with quantitative real-time PCR. The expression of sterol regulatory element binding protein 1c (SREBP1c), acetyl-CoA carboxylase 2 (ACC2), diacylglycerol acyltransferase (DGAT1), and nuclear respiration factor (NRF) was higher in the lowest two quartiles of S(I) (<50th) compared with the highest two quartiles of S(I) (>50th). Interestingly, peroxisome proliferator-activated receptor coactivator 1 alpha (PGC1 alpha), peroxisome proliferator-activated receptor alpha (PPAR alpha), and muscle carnitine palmitoyl transferase 1b (mCPT1), important for oxidative metabolism, showed a complex mRNA expression profile; levels were lower in both the most "insulin sensitive" (IS) as well as the most "IR" individuals. Lipoprotein lipase (LPL) mRNA was reduced in the lowest quartile of S(I). Enhanced gene expression of SREBP1c and ACC2 in the IR state suggests a tendency towards FA storage rather than oxidation. From the lower expression of PGC1 alpha, PPAR alpha, and mCPT1 in both the most "IS" as well as the most "IR" individuals, it may be speculated that "IS" subjects do not need to upregulate these genes to have a normal FA oxidation, whereas the most "IR" individuals are inflexible in upregulating these genes.
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