Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, Orlando, FL.
J Lipid Res. 2014 Feb;55(2):247-57. doi: 10.1194/jlr.M043422. Epub 2013 Nov 20.
Liver X receptors (LXRs) are transcription factors known for their role in hepatic cholesterol and lipid metabolism. Though highly expressed in fat, the role of LXR in this tissue is not well characterized. We generated adipose tissue LXRα knockout (ATaKO) mice and showed that these mice gain more weight and fat mass on a high-fat diet compared with wild-type controls. White adipose tissue (WAT) accretion in ATaKO mice results from both a decrease in WAT lipolytic and oxidative capacities. This was demonstrated by decreased expression of the β2- and β3-adrenergic receptors, reduced level of phosphorylated hormone-sensitive lipase, and lower oxygen consumption rates (OCRs) in WAT of ATaKO mice. Furthermore, LXR activation in vivo and in vitro led to decreased adipocyte size in WAT and increased glycerol release from primary adipocytes, respectively, with a concomitant increase in OCR in both models. Our findings show that absence of LXRα in adipose tissue results in elevated adiposity through a decrease in WAT oxidation, secondary to attenuated FA availability.
肝 X 受体 (LXRs) 是转录因子，其在肝脏胆固醇和脂质代谢中发挥作用。尽管在脂肪中高度表达，但 LXR 在该组织中的作用尚未得到很好的描述。我们生成了脂肪组织 LXRα 敲除 (ATaKO) 小鼠，并表明与野生型对照相比，这些小鼠在高脂肪饮食中体重和脂肪量增加更多。ATaKO 小鼠的白色脂肪组织 (WAT) 积累是由于 WAT 脂肪分解和氧化能力下降所致。这表现在 ATaKO 小鼠的 WAT 中 β2-和 β3-肾上腺素能受体表达减少、磷酸化激素敏感脂肪酶水平降低以及耗氧量 (OCR) 降低。此外，体内和体外的 LXR 激活分别导致 WAT 中脂肪细胞变小和原代脂肪细胞中甘油释放增加，两种模型中的 OCR 均相应增加。我们的研究结果表明，脂肪组织中 LXRα 的缺失导致脂肪量增加，这是由于 FA 可用性减弱导致 WAT 氧化减少所致。
