Tao H, Aakula S, Abumrad NN, Hajri T
Peroxisome proliferator-activated receptor gamma (PPAR{gamma}) regulates the expression and Function of very low density lipoprotein receptor. [JOURNAL ARTICLE]
Am J Physiol Endocrinol Metab 2009 Oct 27.
Very low density lipoprotein receptor is a member of the low density receptor family, highly expressed in adipose tissue, heart and skeletal muscle. It binds apolipoprotein-E (apo-E)-TG-rich lipoproteins and plays a significant role in triglyceride metabolism. PPARgamma is a primary regulator of lipid metabolism in adipocyte and controls the expression of an array of genes involved in lipid trafficking in adipocytes. However, it is not known whether VLDLR is also under the control of PPARgamma. In this study, we have investigated the role of PPARgamma in the regulation of VLDLR expression and function in vivo and in vitro. During the differentiation of 3T3-L1 preadipocytes, the levels of VLDLR protein and mRNA increased in parallel to the induction of PPARgamma expression, and reached a maximum in mature adipocyte. Treatment of differentiated adipocytes with PPARgamma agonist pioglitazone upregulated VLDLR expression in dose- and time-dependent manners. In contrast, specific inhibition of PPARgamma significantly downregulated the protein level of VLDLR. Induction of VLDLR is also demonstrated in vivo in adipose tissue of wild type (WT) mice treated with pioglitazone. In addition, pioglitazone increased plasma TG-rich lipoprotein clearance and increased epididymal fat mass in WT mice, but failed to induce similar effects in vldlr(-/-) mice. These results were further corroborated by the finding that pioglitazone treatment enhanced adipogenesis and lipid deposition in preadipocytes of WT mice, while its effect in VLDLR null preadipocytes was significantly blunted. These findings provide direct evidence that VLDLR expression is regulated by PPARgamma and contributes in lipid uptake and adipogenesis.
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