Endogenous ApoE expression modulates adipocyte triglyceride content and turnover.

Apolipoprotein E (apoE) is highly expressed in adipose tissue and adipocytes in which its expression is regulated by peroxisome proliferator-activated receptor (PPAR)-gamma agonists and tumor necrosis factor-alpha. There is, however, no information regarding a role for endogenous apoE in differentiated adipocyte function. In this report, we define a novel role for apoE in modulating adipocyte lipid metabolism. ApoE(-/-) mice have less body fat and smaller adipocytes compared with wild-type controls. Freshly isolated adipose tissue from apoE(-/-) mice contains lower levels of triglyceride and free fatty acid, and these differences are maintained in cultured adipocytes derived from preadipocytes. Adenoviral expression of apoE in apoE(-/-)-cultured adipocytes increases triglyceride and fatty acid content. During incubation with apoE-containing triglyceride-rich lipoproteins, apoE(-/-) adipose tissue accumulates less triglyceride than wild type. The absence of apoE expression in primary cultured adipocytes also leads to changes in the expression of genes involved in the metabolism/turnover of fatty acids and the triglyceride droplet. Markers of adipocyte differentiation were lower in freshly isolated and cultured apoE(-/-) adipocytes. Importantly, PPAR-gamma-mediated changes in lipid content and gene expression are markedly altered in cultured apoE(-/-) adipocytes. These results establish a novel role for endogenous apoE in adipocyte lipid metabolism and have implications for constructing an integrated model of adipocyte physiology in health and disease.