on July 3, 2003
Published online before print July 3, 2003, doi: 10.1161/01.ATV.0000085040.58340.36
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Submitted on April 7, 2003
Accepted on June 13, 2003
VLDL Induces Adipocyte Differentiation in ApoE-Dependent Manner
Tsuyoshi Chiba ;
From Tokyo Medical and Dental University Graduate School, Vascular Medicine and Geriatrics, Tokyo, Japan.
* To whom correspondence should be addressed. 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--However, 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.
Conclusions--In fact, lipid components of VLDL or free fatty acids induced only partial adipogenesis. 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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