Abstract 142: Effects of Omega-3 Fatty Acids on 3T3-L1 Preadipocyte Differentiation and Inflammatory Response

Abstract

Objective: Adipose tissue (AT)-specific inflammation in obesity is associated with several metabolic disorders such as insulin resistance, and hepatic steatosis. We and others have shown that fish oil containing the omega-3 fatty acids increases AT mass in animal models which is associated with reduced AT-inflammation, hepatic steatosis, and dyslipidemia. Therefore, the objective of this study is to determine whether the omega-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) induce the differentiation process in 3T3-L1 preadipocytes. Methods: 3T3-L1 cells were pretreated and differentiated in the presence of different long chain fatty acids such as oleic acid (OA), stearic acid (SA), EPA, DHA, or a mixture of EPA and DHA (E+D) at a concentration of 50 μM. Results: Oil red O staining revealed that the differentiation process was remarkably increased in cells treated with DHA and, to a lesser extent with SA, compared to control cells differentiated in the absence of fatty acids. Real time PCR analysis showed that the expression of aP2, a marker of preadipocyte differentiation, was increased significantly in cells treated with DHA (4.1-fold, P <0.001) or SA (2.8-fold, p<0.05), compared to undifferentiated control cells. DHA and E+D but not SA increased the expression of cEBP alpha, another marker of differentiation (8.0-fold and 6.2-fold in DHA and E+D, respectively, P <0.001). EPA and OA did not increase the expression of these differentiation markers. SA but not DHA-mediated increase in preadipocyte differentiation was associated with an increase in the expression of MCP-1, an inflammatory marker (1.9-fold, P <0.05). Analysis of MAPK pathways that modulate cell differentiation and inflammation showed that treatment with DHA but not other fatty acids, led to a significant decrease in the phosphorylation of ERK1/2 and p38 MAPK compared to differentiated control cells. Conclusions: Our data demonstrate that EPA and DHA have differential effects with regard to the differentiation of preadipocytes. Our data also show that unlike SA, the differentiation induced by DHA is not associated with an activation of inflammatory pathways suggesting that this effect of DHA is beneficial in improving the lipid storage function of AT.