LDL receptor deficiency unmasks altered VLDL triglyceride metabolism in VLDL receptor transgenic and knockout mice

The very low density lipoprotein receptor (VLDLR) has been proposed to play a role in the delivery of fatty acids to peripheral tissues. However, despite reduced adi- pose tissue mass in VLDLR-deficient ( VLDLR 2 / 2 ) mice, this has been difficult to substantiate. In the present study, VLDLR-deficient and VLDLR-overexpressing (PVL) mice were cross-bred onto a low density lipoprotein receptor knockout ( LDLR 2 / 2 ) background to study the VLDLR under conditions of relatively high serum VLDL and triglyceride levels. Absence of the VLDLR resulted in a significant in- crease in serum triglyceride levels (1.9-fold) when mice were fed a high fat diet. In contrast, overexpression of the VLDLR resulted in a significant decrease in serum triglycer- ide levels (2.0-fold) under similar conditions. When kept on a chow diet, a period of prolonged fasting revealed a signif- icant increase in serum triglyceride levels in VLDLR 2 / 2 ; LDLR 2 / 2 mice (2.3-fold) as compared with LDLR 2 / 2 con- trols. This could not be attributed to altered apolipoprotein B and VLDL triglyceride production rates. Furthermore, no major differences in nascent VLDL triglyceride content were found between VLDLR 2 / 2 ; LDLR 2 / 2 mice and LDLR 2 / 2 controls. However, the triglyceride content of circulating VLDL of VLDLR 2 / 2 ; LDLR 2 / 2 mice (63%) was relatively high as compared with LDLR 2 / 2 controls (49%). These ob-