Apolipoprotein E (apoE), a key regulator of lipid metabolism, is highly produced by adipose tissue and adipocytes. However, there is little information about its role on adipocyte functions. Because apoE-deficiency in adipocytes was shown to impair adipocyte differentiation, we investigated the consequences of apoE high expression on differentiation and proliferation of a human adipocytic cell line (SW872). SW872 cells were transfected with human apoE to induce a fivefold increase in apoE production and secretion. Adipocyte differentiation and proliferation were assayed by measuring lipid content, adipogenic gene expression, cell number, cell resistance to serum deprivation, and cell division kinetics. Cultured apoE-transfected cells accumulated less triglycerides and less cholesterol than control cells. This decrease in lipid accumulation was associated with a strong downregulation of peroxisome proliferator-activated receptors γ1 and γ2 and stearoyl-CoA desaturase 1. The decrease in lipid accumulation was not dependent on the presence of lipids, lipoproteins, or PPAR-γ agonists in the culture medium, nor was it observed with exogenously added apoE. Moreover, we observed that apoE-transfected cells were more resistant to death induced by serum deprivation, and that these cells underwent more cell divisions than control cells. These results bring new evidence of apoE-involvement in metabolic disorders at the adipocyte level. J. Cell. Biochem. 106: 608–617, 2009. © 2009 Wiley-Liss, Inc.