出版社：American Society for Biochemistry and Molecular Biology
摘要：The liver X receptors α and β (LXRα and LXRβ) have been shown to play important roles in lipid homeostasis in liver and macrophages, however, their function in adipose tissue is not well defined. Both LXRs are highly expressed in fat, and the expression of LXRα increases during adipogenesis. Furthermore, LXRα expression is induced by peroxisome proliferator-activated receptor γ (PPARγ), the master regulator of fat cell differentiation. Here we investigate the role of LXRs in adipocyte differentiation and gene expression and their potential crosstalk with the PPARγ pathway. We demonstrate that LXR agonists have no significant effect on the differentiation of 3T3-F442A or 3T3-L1 preadipocytes in vitro and do not alter the expression of differentiation-linked PPARγ target genes in vivo. Moreover, retroviral expression of LXRα in NIH-3T3 cells does not alter the adipogenic potential of these cells and neither augments nor inhibits the action of PPARγ. However, transcriptional profiling studies reveal that LXRs are important regulators of adipocyte gene expression. We identify the multifunction lipid carrier protein apolipoprotein D and the lipogenic protein Spot 14 as LXR responsive genes both in vitro and in vivo. Thus, although LXRs do not influence adipocyte differentiation per se, these receptors are likely to play an important role in the modulation of lipid metabolism in adipocytes.
