Juvet Lene K, Andresen Sissel M, Schuster Gertrud U, Dalen Knut Tomas, Tobin Kari Anne R, Hollung Kristin, Haugen Fred, Jacinto Severina, Ulven Stine M, Bamberg Krister, Gustafsson Jan-Ake, Nebb Hilde I
Institute for Nutrition Research, University of Oslo, N-0316 Oslo, Norway.
Mol Endocrinol. 2003 Feb;17(2):172-82. doi: 10.1210/me.2001-0210.
The pivotal role of liver X receptors (LXRs) in the metabolic conversion of cholesterol to bile acids in mice is well established. More recently, the LXRalpha promoter has been shown to be under tight regulation by peroxisome proliferator-activated receptors (PPARs), implying a role for LXRalpha in mediating the interplay between cholesterol and fatty acid metabolism. We have studied the role of LXR in fat cells and demonstrate that LXR is regulated during adipogenesis and augments fat accumulation in mature adipocytes. LXRalpha expression in murine 3T3-L1 adipocytes as well as in human adipocytes was up-regulated in response to PPARgamma agonists. Administration of a PPARgamma agonist to obese Zucker rats also led to increased LXRalpha mRNA expression in adipose tissue in vivo. LXR agonist treatment of differentiating adipocytes led to increased lipid accumulation. An increase of the expression of the LXR target genes, sterol regulatory binding protein-1 and fatty acid synthase, was observed both in vivo and in vitro after treatment with LXR agonists for 24 h. Finally, we demonstrate that fat depots in LXRalpha/beta-deficient mice are smaller than in age-matched wild-type littermates. These findings imply a role for LXR in controlling lipid storage capacity in mature adipocytes and point to an intriguing physiological interplay between LXR and PPARgamma in controlling pathways in lipid handling.
肝脏X受体（LXRs）在小鼠体内胆固醇向胆汁酸的代谢转化过程中所起的关键作用已得到充分证实。最近研究发现，LXRα启动子受过氧化物酶体增殖物激活受体（PPARs）的严格调控，这意味着LXRα在介导胆固醇与脂肪酸代谢之间的相互作用中发挥作用。我们研究了LXR在脂肪细胞中的作用，结果表明LXR在脂肪生成过程中受到调控，并能促进成熟脂肪细胞中的脂肪积累。PPARγ激动剂可使小鼠3T3 - L1脂肪细胞以及人脂肪细胞中的LXRα表达上调。给肥胖的Zucker大鼠注射PPARγ激动剂也会导致其体内脂肪组织中LXRα mRNA表达增加。用LXR激动剂处理分化中的脂肪细胞会导致脂质积累增加。在用LXR激动剂处理24小时后，在体内和体外均观察到LXR靶基因——固醇调节结合蛋白-1和脂肪酸合酶的表达增加。最后，我们证明LXRα/β基因敲除小鼠的脂肪库比年龄匹配的野生型同窝小鼠小。这些发现表明LXR在控制成熟脂肪细胞的脂质储存能力中发挥作用，并指出LXR与PPARγ在控制脂质处理途径方面存在有趣的生理相互作用。
