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 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.
Goudriaan
J R
JR
TNO-Prevention and Health, Gaubius Laboratory, and MGC-Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Tacken
P J
PJ
Dahlmans
V E
VE
Gijbels
M J
MJ
van Dijk
K W
KW
Havekes
L M
LM
Jong
M C
MC
D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000818:Animals; D004036:Diet, Atherogenic; D005227:Fatty Acids / Q000378:metabolism; D005951:Glucose Tolerance Test; D007333:Insulin Resistance; D051379:Mice; D018345:Mice, Knockout; D008820:Mice, Obese; D008822:Mice, Transgenic; D009765:Obesity / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D011973:Receptors, LDL / Q000235:genetics*; D014280:Triglycerides / Q000097:blood; D015430:Weight Gain
D005227:Fatty Acids; D011973:Receptors, LDL; D014280:Triglycerides; C036053:VLDL receptor