Retinaldehyde dehydrogenase 1 regulates a thermogenic program in white adipose tissue.
Retinaldehyde dehydrogenase 1 regulates a thermogenic program in white adipose tissue.
复制标题
视网膜甲醛脱氢酶1调节白色脂肪组织中的热程序。
作者：
促进棕色脂肪组织（BAT）的形成和功能可以减少肥胖。最近的数据将类维生素a与能量平衡联系起来，但在白色脂肪和棕色脂肪中，类维生素a代谢的具体作用尚不清楚。视黄醛脱氢酶（Aldhs），也被称为醛脱氢酶，是将视黄醛（Rald）转化为视黄酸的限速酶。在这里，我们发现Aldh1a1主要在白色脂肪组织（WAT）中表达，包括小鼠和人类的内脏储存库。Aldh1a1基因缺失在WAT中诱导了类似蝙蝠的转录程序，该程序驱动解偶联呼吸和适应性产热。wat选择性敲低Aldh1a1赋予肥胖小鼠这种BAT程序，限制体重增加并改善葡萄糖稳态。Rald通过选择性激活视黄酸受体（RAR）、募集辅激活因子PGC-1α和诱导Ucp1启动子活性，诱导白色脂肪细胞中解偶联蛋白-1 (Ucp1) mRNA和蛋白水平。这些数据表明Aldh1a1及其底物Rald是以前未被认识的脂肪细胞可塑性和适应性产热的决定因素，这可能具有潜在的治疗意义。
Promoting brown adipose tissue (BAT) formation and function may reduce obesity. Recent data link retinoids to energy balance, but a specific role for retinoid metabolism in white versus brown fat is unknown. Retinaldehyde dehydrogenases (Aldhs), also known as aldehyde dehydrogenases, are rate-limiting enzymes that convert retinaldehyde (Rald) to retinoic acid. Here we show that Aldh1a1 is expressed predominately in white adipose tissue (WAT), including visceral depots in mice and humans. Deficiency of the Aldh1a1 gene induced a BAT-like transcriptional program in WAT that drove uncoupled respiration and adaptive thermogenesis. WAT-selective Aldh1a1 knockdown conferred this BAT program in obese mice, limiting weight gain and improving glucose homeostasis. Rald induced uncoupling protein-1 (Ucp1) mRNA and protein levels in white adipocytes by selectively activating the retinoic acid receptor (RAR), recruiting the coactivator PGC-1α and inducing Ucp1 promoter activity. These data establish Aldh1a1 and its substrate Rald as previously unrecognized determinants of adipocyte plasticity and adaptive thermogenesis, which may have potential therapeutic implications.
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DOI：
10.1097/med.0b013e328337a81f
发表时间：
2010-04
期刊：
Current opinion in endocrinology, diabetes, and obesity
影响因子：
--
作者：
Cypess AM;Kahn CR
通讯作者：
Kahn CR
影响因子：
64.5
作者：
Puigserver, P;Wu, ZD;Spiegelman, BM
通讯作者：
Spiegelman, BM
影响因子：
5.3
作者：
Kane, Maureen A.;Folias, Alexandra E.;Napoli, Joseph L.
通讯作者：
Napoli, Joseph L.
影响因子：
64.5
作者：
Schug, Thaddeus T.;Berry, Daniel C.;Noy, Noa
通讯作者：
Noy, Noa
DOI：
10.1073/pnas.0603806103
发表时间：
2006-08-01
影响因子：
11.1
作者：
Chute, John P.;Muramoto, Garrett G.;McDonnell, Donald P.
通讯作者：
McDonnell, Donald P.