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- Garcia-Rios, Antonio, et al.
(author)
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Genetic variations at the lipoprotein lipase gene influence plasma lipid concentrations and interact with plasma n-6 polyunsaturated fatty acids to modulate lipid metabolism
- 2011
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In: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 218:2, s. 416-422
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Journal article (peer-reviewed)abstract
- Objective: To investigate whether seven common single nucleotide polymorphisms (SNPs) at the lipoprotein lipase (LPL) locus interact with total plasma fatty acids to modulate plasma lipid metabolism in metabolic syndrome (MetS) patients. Methods: Plasma fatty acid composition, plasma lipid concentrations and LPL SNPs were determined in 452 subjects with the MetS in the European LIPGENE human study and were repeated in 1754 subjects from the LIPGENE-SU.VI.MAX Study. Results: Triglycerides (TG) were lower, and HDL higher in the carriers of rs328 and rs1059611 in the SUVIMAX cohort (all P < 0.001), and these findings showed a similar, non-significant trend in LIPGENE cohort. In this last cohort, we found a gene-fatty acids interaction, as the carriers of the minor allele displayed a lower fasting TG and triglyceride rich lipoproteins-TG (TRL-TG) concentrations only when they had n-6 polyunsaturated fatty acids below the median (all P < 0.05). Moreover, subjects carrying the minor allele for rs328 SNP and with a low level of n-6 PUFA displayed higher nonesterified fatty acid (NEFA) plasma concentrations as compared with homozygous for the major allele (P = 0.034). Interestingly, the n-6 PUFA-dependent associations between those SNPs and TG metabolism were also replicated in subjects without MetS from the SU.VI.MAX cohort. Conclusion: Two genetic variations at the LPL gene (rs328 and rs1059611) influence plasma lipid concentrations and interact with plasma n-6 PUFA to modulate lipid metabolism. The knowledge of new genetic factors together with the understanding of these gene-nutrient interactions could help to a better knowledge of the pathogenesis in the MetS.
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- Jans, Anneke, et al.
(author)
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Transcriptional Metabolic Inflexibility in Skeletal Muscle Among Individuals With Increasing Insulin Resistance
- 2011
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In: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 19:11, s. 2158-2166
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Journal article (peer-reviewed)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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3. |
- Paniagua, J. A., et al.
(author)
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A low-fat high-carbohydrate diet supplemented with long-chain n-3 PUFA reduces the risk of the metabolic syndrome
- 2011
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In: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 218:2, s. 443-450
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Journal article (peer-reviewed)abstract
- Objective: Dietary changes are major factor in determining cardiovascular risk. We assessed the effects of isoenergetic diets with different fat quantity and quality on the incidence and regression of the metabolic syndrome (MetS) from the LIPGENE project. Methods and design: Clinical intervention study: the patients (n = 337) were randomly assigned to one of four diets for 12 weeks each: two high fat diets, one rich in saturated fat (HSFA) and the other rich in monounsaturated fat (HMUFA), and two low fat diets, one high in complex carbohydrates (LFHCC) supplemented with 1.24 g/day of long-chain n-3 polyunsaturated fatty acids (LFHCC n-3) and the other LFHCC diet with placebo (LFHCC). Measurements: the effects on MetS risk criteria were recorded before and after the intervention period. Results: An enlarged waist circumference (>= 88 cm for women and >= 102 cm for men) was present among 95% of the participants, 88% had elevated blood pressure (>130/85 mm Hg or antihypertensive drugs), 77% had elevated fasting plasma glucose (>= 5.55 mmol/L), 51% were hypertriacylglycerolemic (>= 1.7 mmol/L), and 72% had low HDL cholesterol (<1.0 mmol/L for men, and <1.3 mmol/L for women). The prevalence of enlarged waist circumference, hypertension and hypertriacylglycerolemia were reduced after the LFHCC n-3 diet (p<0.05). Thus the prevalence of MetS fell by 20.5% after LFHCC n-3 diet compared with the HSFA (10.6%), HMUFA (12%) diet or LFHCC (10.4%) diets (p<0.028). Conclusions: The consumption of a low-fat high-carbohydrate supplemented with n-3 diet reduced the risk of MetS as compared with isoenergetic high-fat (HSFA and HMUFA) and LFHCC diets.
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