Published online before print July 3, 2003, doi: 10.1161/01.ATV.0000085040.58340.36
© 2003 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
VLDL Induces Adipocyte Differentiation in ApoE-Dependent Manner
From Tokyo Medical and Dental University Graduate School, Vascular Medicine and Geriatrics, Tokyo, Japan.
Correspondence to Kentaro Shimokado, MD, Vascular Medicine and Geriatrics, Tokyo Medical and Dental University Graduate School, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8619 Japan. E-mail k.shimoka.vasc{at}tmd.ac.jp
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. Tetrahydrolipstatin, a lipoprotein lipase inhibitor, did not affect the adipogenic activity of VLDL, suggesting that hydrolysis of VLDL did not play a major role in its effects. In fact, lipid components of VLDL or free fatty acids induced only partial adipogenesis.
Conclusions— Our findings indicate that VLDL induces adipogenesis in an apoE-dependent manner both in vitro and in vivo.
Key Words: VLDL • apolipoprotein E • lipoprotein lipase • obesity • adipogenesis
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