Endogenous ApoE Expression Modulates Adipocyte Triglyceride Content and Turnover

Abstract

Apolipoprotein E (apoE) is highly expressed in adipose tissue and adipocytes in which its expression is regulated by peroxisome proliferator–activated receptor (PPAR)-γ agonists and tumor necrosis factor–α. 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-γ–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.