Oestrogen signalling in white adipose progenitor cells inhibits differentiation into brown adipose and smooth muscle cells.
Oestrogen signalling in white adipose progenitor cells inhibits differentiation into brown adipose and smooth muscle cells.
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DOI：
10.1038/ncomms6196
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发表时间：
2014-10-21
影响因子：
16.6
通讯作者：
Graff JM
中科院分区：
文献类型：
--
作者：
Lapid K;Lim A;Clegg DJ;Zeve D;Graff JM
雌激素通常通过雌激素受体α(ERα)信号调节代谢生理，突出表现为绝经后体温失调(潮热)、糖耐量异常、食欲增加和代谢率降低。在这里，我们展示了ERα信号在小鼠脂肪谱系规范中的作用。ERα调节脂肪前体的身份和潜能，促进白色成脂血统的承诺。缺乏ERα的白色脂肪前体细胞重新编程，进入平滑肌和棕色成脂命运。机械学研究强调了转化生长因子β计划参与了ERα信号下游的前体重新编程。观察到的重新编程具有深远的代谢结果；雌性和雄性脂肪系ERα突变小鼠都很瘦，对葡萄糖的敏感度提高，并且对高脂饮食中的体重增加具有抵抗力。此外，它们具有高代谢、高摄食性和高温性，都与棕色表型一致。综上所述，这些发现表明，ERα细胞以一种与普遍的代谢性疾病相关的方式自主地调节脂肪谱系承诺、棕色脂肪和平滑肌细胞的形成以及系统代谢。
Oestrogen, often via oestrogen receptor alpha (ERα) signalling, regulates metabolic physiology, highlighted by post-menopausal temperature dysregulation (hot flashes), glucose intolerance, increased appetite and reduced metabolic rate. Here we show that ERα signalling has a role in adipose lineage specification in mice. ERα regulates adipose progenitor identity and potency, promoting white adipogenic lineage commitment. White adipose progenitors lacking ERα reprogramme and enter into smooth muscle and brown adipogenic fates. Mechanistic studies highlight a TGFβ programme involved in progenitor reprogramming downstream of ERα signalling. The observed reprogramming has profound metabolic outcomes; both female and male adipose-lineage ERα-mutant mice are lean, have improved glucose sensitivity and are resistant to weight gain on a high-fat diet. Further, they are hypermetabolic, hyperphagic and hyperthermic, all consistent with a brown phenotype. Together, these findings indicate that ERα cell autonomously regulates adipose lineage commitment, brown fat and smooth muscle cell formation, and systemic metabolism, in a manner relevant to prevalent metabolic diseases.