孤儿核受体SHP调节棕色脂肪细胞中PGC-1α的表达和能量产生。
The orphan nuclear receptor SHP regulates PGC-1alpha expression and energy production in brown adipocytes.
作者信息
Wang Li, Liu Jun, Saha Pradip, Huang Jiansheng, Chan Lawrence, Spiegelman Bruce, Moore David D
机构信息
Department of Medicine, The University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
出版信息
Cell Metab. 2005 Oct;2(4):227-38. doi: 10.1016/j.cmet.2005.08.010.
Brown adipocytes increase energy production in response to induction of PGC-1alpha, a dominant regulator of energy metabolism. We have found that the orphan nuclear receptor SHP (NR0B2) is a negative regulator of PGC-1alpha expression in brown adipocytes. Mice lacking SHP show increased basal expression of PGC-1alpha, increased energy expenditure, and resistance to diet-induced obesity. Increased PGC-1alpha expression in SHP null brown adipose tissue is not due to beta-adrenergic activation, since it is also observed in primary cultures of SHP(-/-) brown adipocytes that are not exposed to such stimuli. In addition, acute inhibition of SHP expression in cultured wild-type brown adipocytes increases basal PGC-1alpha expression, and SHP overexpression in SHP null brown adipocytes decreases it. The orphan nuclear receptor ERRgamma is expressed in BAT and its transactivation of the PGC-1alpha promoter is potently inhibited by SHP. We conclude that SHP functions as a negative regulator of energy production in BAT.
棕色脂肪细胞会响应能量代谢的主要调节因子PGC-1α的诱导而增加能量产生。我们发现孤儿核受体SHP（NR0B2）是棕色脂肪细胞中PGC-1α表达的负调节因子。缺乏SHP的小鼠表现出PGC-1α基础表达增加、能量消耗增加以及对饮食诱导的肥胖具有抗性。SHP缺失的棕色脂肪组织中PGC-1α表达增加并非由于β-肾上腺素能激活，因为在未暴露于此类刺激的SHP（-/-）棕色脂肪细胞原代培养物中也观察到了这种情况。此外，在培养的野生型棕色脂肪细胞中急性抑制SHP表达会增加基础PGC-1α表达，而在SHP缺失的棕色脂肪细胞中过表达SHP则会降低其表达。孤儿核受体ERRγ在棕色脂肪组织中表达，并且其对PGC-1α启动子的反式激活受到SHP的强烈抑制。我们得出结论，SHP作为棕色脂肪组织中能量产生的负调节因子发挥作用。
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