Adipocytes isolated from apoE knockout mice display alterations in triglyceride metabolism and gene expression. The current studies were undertaken to evaluate the impact of endogenously produced adipocyte apoE on these adipocyte parameters in vivo, independent of the profoundly disturbed metabolic milieu of apoE knockout mice. Adipose tissue from wild-type or apoE knockout mice was transplanted into wild-type recipients followed by 8-10 weeks of chow or high-fat diet. After a chow diet, freshly isolated transplanted apoE adipocytes were significantly (70%) smaller (P < 0.05) than transplanted wild-type adipocytes and displayed significantly lower rates of triglyceride synthesis and higher rates of triglyceride hydrolysis. Transplanted apoE knockout adipocytes also had higher mRNA levels for adiponectin, perilipin and genes coding for enzymes in the fatty acid oxidation pathway, and lower levels of caveolin. After a high-fat diet, and consequent increase in circulating lipid and apoE levels, transplanted wild-type adipocyte size increased by 106x10³µm³; while apoE knockout adipocyte size increased only by 19x10³µm³. Endogenous host adipose tissue harvested from wild-type recipients of transplanted wild-type or apoE knockout adipose tissue did not demonstrate any difference in adipocyte size. Consistent with the in vivo observations, apoE knockout adipocytes synthesized less triglyceride when incubated with apoE-containing triglyceride-rich lipoproteins compared to wild-type adipocytes. Our results establish a novel in vivo role for endogenously produced apoE, distinct from circulating apoE, in modulation of adipocyte triglyceride metabolism and gene expression. They support a model in which endogenously produced adipocyte apoE facilitates adipocyte lipid acquisition from circulating triglyceride-rich lipoproteins.