DHA increases adiponectin expression more effectively than EPA at relative low concentrations by regulating PPARγ and its phosphorylation at Ser273 in 3T3-L1 adipocytes

Background: Enhancing circulating adiponectin is considered as a potential approach for the prevention and treatment of non-communicable diseases (NCDs). Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were reported to increase adiponectin by previous studies using a mixture of them. However, their individual effects on adiponectin and the underlying mechanisms are still unclear. In the present study, we observed and compared the individual effect of DHA and EPA on adiponectin in 3T3-L1 adipocytes, and further tested whether DHA or EPA regulated adiponectin by peroxisome proliferator-activated receptor. (PPAR gamma) and its phosphorylation at Ser273 to provide a plausible explanation for their distinct actions. Methods: Firstly, 3T3-L1 adipocytes were treated with different doses of DHA or EPA for 24 h. Secondly, 3T3-L1 adipocytes were treated with DHA or EPA in the presence or absence of GW9662. Thirdly, 3T3-L1 adipocytes were pretreated with DHA or EPA for 24 h, followed by being respectively co-incubated with tumor necrosis factor a (TNF-alpha) or roscovitine for another 2 h. Bovine serum albumin treatment served as the control. After treatments, cellular and secreted adiponectin, cellular PPAR. and its phosphorylation at Ser273 were determined. Results: Compared with the control, DHA increased cellular and secreted adiponectin at 50 and 100 mu mol/L, while EPA increased them at 100 and 200 mu mol/L. Adiponectin expressions in DHA treated groups were significantly higher than those in EPA treated groups at 50 and 100 mu mol/L. Both DHA and EPA enhanced PPAR. expression, but DHA was more effective. GW9662 blocked DHA-and EPA-induced increases in PPAR. as well as adiponectin. Remarkably, an opposite regulation of PPAR. phosphorylation was detected after fatty acids treatment: DHA inhibited it but EPA stimulated it. TNF-alpha blocked DHA-induced decrease in PPAR. phosphorylation, which eventually led to a decrease in adiponectin. Roscovitine blocked EPA-induced increase in PPAR. phosphorylation, but the corresponding increase in adiponectin was non-significant. Conclusion: DHA compared with EPA led to a greater increase in cellular and secreted adiponectin at relative low concentrations by increasing PPAR. expression and inhibiting its phosphorylation at Ser273. DHA may be more beneficial than EPA in reducing risks of NCDs.