Effect of interaction betweenPPARG,PPARAandADIPOQgene variants and dietary fatty acids on plasma lipid profile and adiponectin concentration in a large intervention study

Abstract

Unsaturated fatty acids are ligands of PPAR-γ, which up-regulates genes involved in fatty acid transport and TAG synthesis and the insulin-sensitising adipokine adiponectin, which activates fatty acid β-oxidation via PPAR-α action in liver. We investigated the effect of dietary fatty acid interaction withPPARG, PPARAandADIPOQgene variants on plasma lipid and adiponectin concentrations in the Reading Imperial Surrey Cambridge King's study, a five-centre, parallel design, randomised controlled trial of 466 subjects at increased cardiometabolic risk. After a 4-week run-in to baseline, SFA was replaced by MUFA or carbohydrate (low fat) in isoenergetic diets for 24 weeks. Habitual dietary PUFA:SFA ratio×PPARGPro12Ala genotype interaction influenced plasma total cholesterol (P=0·02), LDL-cholesterol (P=0·002) and TAG (P=0·02) concentrations in White subjects.PPARAVal162Leu×PPARGPro12Ala genotype interaction influenced total cholesterol (P=0·04) and TAG (P=0·03) concentrations at baseline. After high-MUFA and low-fat diets, total cholesterol and LDL-cholesterol were reduced (P<0·001) and gene×gene interaction determined LDL-cholesterol (P=0·003) and small dense LDL as a proportion of LDL (P=0·012). At baseline,ADIPOQ−10066 G/A A-allele was associated with lower serum adiponectin (n360;P=0·03) in White subjects. After the high-MUFA diet, serum adiponectin increased in GG subjects and decreased in A-allele carriers (P=0·006 for difference). In GG, adiponectin increased with age after the high MUFA and decreased after the low-fat diet (P=0·003 for difference at 60 years). In conclusion, in Whites, high dietary PUFA:SFA would help to reduce plasma cholesterol and TAG inPPARGAla12 carriers. InADIPOQ−10066 GG homozygotes, a high-MUFA diet may help to increase adiponectin with advancing age.