Liver X receptors are regulators of adipocyte gene expression but not differentiation identification of apoD as a direct target

The liver X receptorsand � (LXRand LXR � ) have been shown to play important roles in lipid homeosta- sis in liver and macrophages, however, their function in adi- pose tissue is not well defined. Both LXRs are highly ex- pressed in fat, and the expression of LXRincreases during adipogenesis. Furthermore, LXRexpression is induced by peroxisome proliferator-activated receptor � (PPAR � ), the master regulator of fat cell differentiation. Here we investigate the role of LXRs in adipocyte differen- tiation and gene expression and their potential crosstalk with the PPARpathway. 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 PPARtarget genes in vivo. Moreover, retroviral expression of LXRin NIH-3T3 cells does not alter the adipogenic potential of these cells and neither augments nor inhibits the action of PPAR � . However, transcriptional profiling studies reveal that LXRs are important regulators of adipocyte gene expression. We identify the multifunction lipid carrier protein apolipopro- tein 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 recep- tors are likely to play an important role in the modulation of lipid metabolism in adipocytes.— Hummasti, S., B. A. Laf- fitte, M. A. Watson, C. Galardi, L. C. Chao, L. Ramamurthy, J. T. Moore, and P. Tontonoz. Liver X receptors are regula- tors of adipocyte gene expression but not differentiation: identification of apoD as a direct target. J. Lipid Res. 2004. 45: 616-625.