Dietary, Genetic and Metabolic Determinants of Serum Adiponectin

Student thesis: Doctoral ThesisDoctor of Philosophy


The role of adiponectin, a cytokine produced in adipose tissue and its relationship to risk factors for the metabolic syndrome, and dietary influences on its production are reviewed. The thesis examines the hypothesis that the amount and type of fatty acids in the diet affect serum adiponectin concentrations. The effects of ADIPOQ gene locus on serum adiponectin concentrations were examined in participants of the RISCK study at baseline and following dietary intervention. Major effects of age, BMI, gender and ethnicity on serum adiponectin were found. At baseline the ADIPOQ +276 G/T T-allele was associated with higher serum adiponectin. The ADIPOQ -10066 G/A A-allele was associated with lower serum adiponectin. No influences were observed for the other SNPs -7734 C/A or -11391. Participants with the -10066 GG genotype showed a 3.8% increase and -10066 A-allele carriers showed a 2.6% decrease in adiponectin (n=360; P=0.006) after a high mononounsaturated fat diet. In-10066 GG homozygotes, adiponectin increased progressively with age after a high monounsaturated fatty acid diet but decreased after a low fat diet. A randomised single-blind parallel study in healthy males (n=48) was conducted to investigate the effects on serum adiponectin concentration of two formulations of DHA and EPA (3 g/d each) versus placebo (refined olive oil) for 6 weeks. Compared to the placebo, neither EPA nor DHA changed serum adiponectin concentration. It was concluded that a high monounsaturated fatty acid diet has a moderate effect on adiponectin concentration and that dietary supplements of long-chain n-3 polyunsaturated fatty acids in healthy subjects have no effect on adiponectin concentration.
Further investigations were conducted to examine the interaction of dietary fatty acid intake with peroxisome proliferator-activated receptor (PPAR) genes. A significant interaction was found between the habitual dietary polyunsaturated/saturated fatty acid ratio and PPARG Pro12Ala genotype on total and LDL cholesterol and plasma triacylglycerol concentrations. After a high monounsaturated fat diet, carriages of both PPARA Val162 and PPARG Ala12 alleles were associated with a greater reduction in plasma LDL-C and its proportion as small dense LDL, than after low fat diet. A significant interactions between n-3 LCP treatment and genotypes of PPARA Leu162Val SNP were found among 310 participants in the MARINA trial. These contributed to a reduction in plasma triacylglycerol concentration with n-3 treatment in subjects homozygous for the more transcriptionally active Leu162 allele. The findings reported in the thesis are discussed in the context of other research in the area.
Date of Award17 Jan 2012
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorThomas Sanders (Supervisor) & Sandra O'Dell (Supervisor)

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