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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1488.)
© 2001 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Protection From Obesity in Mice Lacking the VLDL Receptor

Jeltje R. Goudriaan; Paul J. Tacken; Vivian E.H. Dahlmans; Marion J.J. Gijbels; Ko Willems van Dijk; Louis M. Havekes; Miek C. Jong

From TNO–Prevention and Health, Gaubius Laboratory (J.R.G., V.E.H.D., L.M.H., M.C.J.), and MGC–Department of Human Genetics (P.J.T., M.J.J.G., K.W.v.D.) and the Departments of Cardiology and Internal Medicine (L.M.H.), Leiden University Medical Center, Leiden, The Netherlands.

Correspondence to Prof Dr L.M. Havekes, TNO–Prevention and Health, Gaubius Laboratory, Zernikedreef 9, 2333 CK Leiden, PO Box 2215, 2301 CE Leiden, The Netherlands. E-mail lm.havekes{at}pg.tno.nl

Abstract—— It has previously been reported that mice lacking the VLDL receptor (VLDLR-/-) exhibit normal plasma lipid levels and a modest decrease in adipose tissue mass. In the present study, the effect of VLDLR deficiency on profound weight gain was studied in mice. Obesity was induced either by feeding of a high-fat, high-calorie (HFC) diet or by crossbreeding mice onto the genetically obese ob/ob background. After 17 weeks of HFC feeding, VLDLR-/- mice remained lean, whereas their wild-type littermates (VLDLR+/+) became obese. Similarly, the weight gain of ob/ob mice was less profound in the absence of the VLDLR. Moreover, VLDLR deficiency led to increased plasma triglycerides after HFC feeding. The protection from obesity in VLDLR-/- mice involved decreased peripheral uptake of fatty acids, because VLDLR-/- mice exhibited a significant reduction in whole-body free fatty acid uptake, with no clear differences in food intake and fat absorption. These observations were supported by a strong decrease in average adipocyte size in VLDLR-/- mice of both obesity models, implying reduced adipocyte triglyceride storage in the absence of the VLDLR. These results suggest that the VLDLR plays a role in the delivery of VLDL-derived fatty acids into adipose tissue.

Key Words: VLDL receptor • obesity • fatty acid transport • triglyceride metabolism • transgenic mice

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