Effect of DHA-rich fish oil on PPARγ target genes related to lipid metabolism in type 2 diabetes: A randomized, double-blind, placebo-controlled clinical trial

Background The beneficial effects of omega-3 polyunsaturated fatty acids on lipid levels are well documented. However, the related molecular mechanisms are widely unknown. Omega-3 polyunsaturated fatty acids are natural ligand for peroxisome proliferator-activated receptor γ (PPARγ). Objective The aim of this study was to evaluate the effect of docosahexaenoic acid (DHA)-rich fish oil supplementation on modulation of some PPARγ-responsive genes related to lipid metabolism. Methods Patients with type 2 diabetes were randomly assigned to consume either DHA-rich fish oil (containing 2400 mg/d fish oil; DHA: 1450 mg and eicosapentaenoic acid: 400 mg) or placebo for 8 weeks. Lipid profile and glycemic control parameters as well as the gene expression of PPARγ, liver x receptor-a, ATP-binding cassette A1, and CD36 in peripheral blood mononuclear cells were measured at baseline and after 8 weeks. Results DHA-rich fish oil supplementation resulted in decreased triglycerides (TG) level compared with placebo group, independently of the baseline value of TG (all patients (P = .003), hypertriglyceridemic subjects (P = .01), and normotriglyceridemic subjects (P = .02)). Moreover, a higher reduction in TG level was observed in hypertriglyceridemic subjects, comparing to normotriglyceridemic subjects with DHA-rich fish oil supplementation (P = .01). Other lipid parameters as well as the expression of PPARγ, liver x receptor-a, ATP-binding cassette A1, and CD36 were not affected by DHA-rich fish oil supplementation. Only in hypertriglyceridemic subjects, DHA-rich fish oil supplementation upregulated CD36 expression, compared with the placebo group (P = .01). Conclusions DHA-rich fish oil supplementation for 8 weeks increased CD36 expression in hypertriglyceridemic subjects, which might result to higher reduction in TG level, comparing with normotriglyceridemic subjects. However, this finding should be investigated in further studies. © 2015 National Lipid Association

Docosahexaenoic acid-rich fish oil supplementation improves body composition without influence of the PPARγ Pro12Ala polymorphism in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled clinical trial

Background: The aims of this research were to investigate (1) the impact of docosahexaenoic acid (DHA)-rich fish oil supplementation on body composition, plasma adiponectin level, and peroxisome proliferator-activated receptor γ (PPARγ) gene expression, and (2) whether the effect of DHA-rich fish oil supplementation on the aforementioned variables is modulated by PPARγ Pro12Ala polymorphism. Methods: We genotyped PPARγ Pro12Ala polymorphism in subjects with type 2 diabetes mellitus (T2DM). Ala carriers and non-Ala carriers were randomly assigned to DHA-rich fish oil or placebo intake for 8 weeks. Results: Glycemic control was not affected by the intervention. The supplementation with DHA-rich fish oil decreased waist circumference (p < 0.001), body fat mass (p = 0.01), body fat percent (p = 0.04), and visceral fat rating (p = 0.02) as well as trunk fat mass (p = 0.04). Weight, body mass index, fat-free mass, adiponectin level, and PPARγ gene expression changes showed no significant difference. No gene-diet interaction was found on body composition, adiponectin level, and PPARγ gene expression. Conclusions: DHA-rich fish oil supplementation favorably modulated body composition in patients with T2DM and could be useful to reduce visceral obesity. However, the PPARγ Pro12Ala polymorphism did not influence the changes in the desired variables. © 2015 S. Karger AG, Basel