Protection from obesity in mice lacking the VLDL receptor

It has previously been reported that mice lacking the VLDL receptor (VLDLR- /-) exhibit normal plasma lipid levels and a modest decrease in adipose tis sue 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 geneti cally 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 triglyceri des after HFC feeding. The protection from obesity in VLDLR-/- mice involve d decreased peripheral uptake of fatty acids, because VLDLR-/- mice exhibit ed a significant reduction in whole-body free fatty acid uptake, with no cl ear differences in food intake and fat absorption. These observations were supported by a strong decrease in average adipocyte size in VLDLR-/- mice o f both obesity models, implying reduced adipocyte triglyceride storage in t he absence of the VLDLR. These results suggest that the VLDLR plays a role in the delivery of VLDL-derived fatty acids into adipose tissue.