VLDL induces adipocyte differentiation in ApoE-dependent manner.
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.


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.
Chiba
Tsuyoshi
T
Tokyo Medical and Dental University Graduate School, Vascular Medicine and Geriatrics, Tokyo, Japan.
Nakazawa
Toru
T
Yui
Katsumasa
K
Kaneko
Eiji
E
Shimokado
Kentaro
K
D017667:Adipocytes / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008820:Mice, Obese; D009765:Obesity / Q000150:complications / Q000378:metabolism / Q000473:pathology
D001057:Apolipoproteins E; D005230:Fatty Acids, Nonesterified; D008079:Lipoproteins, VLDL