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.