VLDL Induces Adipocyte Differentiation in ApoE-Dependent Manner

Abstract
Objective— To clarify the role of very low density lipoprotein (VLDL) and apolipoprotein E (apoE) in adipogenesis, we studied newly developed hyperlipidemic obese (ob/ob;apoE−/−) mice. Because hydrolysis of VLDL is believed to be the major source of adipogenic free fatty acids, a higher plasma level of VLDL in these mice should exaggerate obesity. Methods and Results— When fed a high-fat, high-cholesterol diet, ob/ob;apoE−/− mice did not show increased body weight or an increased amount of adipose tissue in spite of increased plasma VLDL levels, whereas ob/ob mice showed an increased body weight and amount of adipose tissue, suggesting that there is a novel apoE-dependent pathway for adipogenesis. In vitro experiments using bone marrow stromal cells and 3T3-L1 cells confirmed this notion. ApoE-deficient VLDL did not induce adipogenesis, whereas normal VLDL induced adipogenesis in these cells. The incubation of apoE-deficient VLDL with recombinant human apoE restored its adipogenic activity. Tetrahydrolips...

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