Pharmacological Activation of Thyroid Hormone Receptors Elicits a Functional Conversion of White to Brown Fat.
Pharmacological Activation of Thyroid Hormone Receptors Elicits a Functional Conversion of White to Brown Fat.
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DOI：
10.1016/j.celrep.2015.10.022
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发表时间：
2015-11-24
期刊：
影响因子：
8.8
通讯作者：
Phillips KJ
中科院分区：
文献类型：
--
作者：
Lin JZ;Martagón AJ;Cimini SL;Gonzalez DD;Tinkey DW;Biter A;Baxter JD;Webb P;Gustafsson JÅ;Hartig SM;Phillips KJ
白色脂肪组织（WAT）向具有棕色脂肪组织（BAT）样活性的组织的功能性转化（通常称为“褐变”）代表了对抗肥胖和代谢疾病的有趣策略。我们证明，甲状腺激素受体（TR）激活的合成激动剂显着诱导一个程序的适应性产热在皮下WAT，与恢复耐寒不耐冷小鼠。与大多数其他布朗宁剂不同，药理学TR活化将WAT的布朗宁与经典BAT的活化分离。TR激动还诱导体外白色脂肪细胞的布朗宁，表明TR介导的布朗宁是细胞自主的。这些数据确立了TR激动剂作为一类布朗宁剂，暗示TR在WAT的布朗宁中，并表明该作用具有深刻的药理学潜力。
The functional conversion of white adipose tissue (WAT) into a tissue with brown adipose tissue (BAT)-like activity, often referred to a ‘browning’, represents an intriguing strategy to combat obesity and metabolic disease. We demonstrate that thyroid hormone receptor (TR) activation by a synthetic agonist markedly induces a program of adaptive thermogenesis in subcutaneous WAT that coincides with a restoration of cold tolerance to cold-intolerant mice. Distinct from most other browning agents, pharmacological TR activation dissociates the browning of WAT from activation of classical BAT. TR agonism also induces the browning of white adipocytes in vitro, indicating that TR mediated browning is cell autonomous. These data establish TR agonists as a class of browning agents, implicate the TRs in the browning of WAT, and suggest a profound pharmacological potential of this action.