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.
Huang
Zhi Hua
ZH
Section of Endocrinology, Diabetes and Metabolism (MC 797), University of Illinois, 1819 W. Polk St., Chicago, IL 60612, USA.
Reardon
Catherine A
CA
Mazzone
Theodore
T
D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000033:anatomy & histology / Q000502:physiology; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D017931:DNA Primers; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005786:Gene Expression Regulation; D051379:Mice; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000235:genetics; D014280:Triglycerides / Q000378:metabolism*
D001057:Apolipoproteins E; D017931:DNA Primers; D005230:Fatty Acids, Nonesterified; D012333:RNA, Messenger; D014280:Triglycerides