Role of adipocyte-derived apoE in modulating adipocyte size, lipid metabolism, and gene expression in vivo

Abstract

Adipocytes isolated from apolipoprotein E (apoE)-knockout (EKO) mice display alterations in triglyceride (TG) metabolism and gene expression. The present 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 EKO mice. Adipose tissue from wild-type (WT) or EKO mice was transplanted into WT recipients, which were then fed chow or high-fat diet for 8–10 wk. After a chow diet, freshly isolated transplanted EKO adipocytes were significantly ( P < 0.05) smaller (70%) than transplanted WT adipocytes and displayed significantly lower rates of TG synthesis and higher rates of TG hydrolysis. Transplanted EKO 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 WT adipocyte size increased by 106 × 103μm3, whereas EKO adipocyte size increased only by 19 × 103μm3. Endogenous host adipose tissue harvested from WT recipients of transplanted WT or EKO adipose tissue did not demonstrate any difference in adipocyte size. Consistent with the in vivo observations, EKO adipocytes synthesized less TG when incubated with apoE-containing TG-rich lipoproteins than WT adipocytes. Our results establish a novel in vivo role for endogenously produced apoE, distinct from circulating apoE, in modulation of adipocyte TG metabolism and gene expression. They support a model in which endogenously produced adipocyte apoE facilitates adipocyte lipid acquisition from circulating TG-rich lipoproteins.