On the role of liver X receptors in lipid accumulation in adipocytes
On the role of liver X receptors in lipid accumulation in adipocytes
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DOI：
10.1210/me.2001-0210
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发表时间：
2003-02-01
影响因子：
--
通讯作者：
Nebb, HI
中科院分区：
文献类型：
--
作者：
Juvet, LK;Andresen, SM;Nebb, HI
肝X受体(LXRs)在小鼠体内胆固醇向胆汁酸的代谢转化中起着关键作用。最近，LXRa启动子被证明受到过氧化体增殖物激活受体(PPAR)的严格调控，这意味着LXRa在调节胆固醇和脂肪酸代谢之间的相互作用中发挥了作用。我们已经研究了LXR在脂肪细胞中的作用，并证明了LXR在脂肪形成过程中受到调控，并促进成熟脂肪细胞中的脂肪积累。PPARγ激动剂可上调小鼠3T3-L1脂肪细胞和人脂肪细胞中LXRa的表达。给肥胖的Zucker大鼠注射PPARGamma激动剂也会导致体内脂肪组织中LXRpha mRNA表达的增加。LXR激动剂处理分化的脂肪细胞导致脂肪堆积增加。在体内和体外，LXR激动剂处理24小时后，LXR靶基因--甾醇调节结合蛋白-1和脂肪酸合成酶的表达都增加。最后，我们证明了LXRα/β缺陷小鼠的脂肪库比年龄匹配的野生型小鼠小。这些发现暗示了LXR在控制成熟脂肪细胞中的脂肪储存能力方面的作用，并指出了LXR和PPARGamma之间在控制脂质处理途径方面的有趣的生理相互作用。
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 LXRa 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. LXRa 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.