Estrogen-Related Receptors Mediate the Adaptive Response of Brown Adipose Tissue to Adrenergic Stimulation.
Estrogen-Related Receptors Mediate the Adaptive Response of Brown Adipose Tissue to Adrenergic Stimulation.
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DOI：
10.1016/j.isci.2018.03.005
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发表时间：
2018-04-27
期刊：
影响因子：
5.8
通讯作者：
Kralli A
中科院分区：
文献类型：
--
作者：
Brown EL;Hazen BC;Eury E;Wattez JS;Gantner ML;Albert V;Chau S;Sanchez-Alavez M;Conti B;Kralli A
肾上腺素能刺激棕色脂肪组织（BAT）诱导急性和长期反应。急性肾上腺素能反应通过解偶联氧化磷酸化和增加底物氧化来激活产热。长期，肾上腺素能信号重塑BAT，诱导适应性转录变化，扩大产热能力。在这里，我们发现雌激素相关受体α和γ（ERRα，ERRγ）是肾上腺素刺激BAT转录重编程的共同关键效应子。缺乏脂肪ERR（ERRαγAd−/−）的小鼠氧化和产热能力降低，暴露于寒冷时迅速体温降低。用β3-肾上腺素能激动剂长期处理的ERRαγAd−/−小鼠不能扩大氧化或产热能力，也不会增加对去甲肾上腺素（NE）的能量消耗。此外，当给予β3-肾上腺素能激动剂时，喂养高脂饮食的ERRαγAd−/−小鼠不会减轻体重或显示葡萄糖耐量改善。这些缺陷的分子基础是发现ERRs介导了肾上腺素能刺激的大量转录反应。脂肪ERRs共同控制棕色脂肪氧化和产热能力脂肪ERRs对β-肾上腺素能激动剂诱导的BAT重塑至关重要ERRs控制对肾上腺素能刺激的大量转录反应缺乏脂肪ERRs的小鼠显示β-肾上腺素能激动剂没有代谢益处肾上腺素能受体功能;生化机制;分子生物学
Adrenergic stimulation of brown adipose tissue (BAT) induces acute and long-term responses. The acute adrenergic response activates thermogenesis by uncoupling oxidative phosphorylation and enabling increased substrate oxidation. Long-term, adrenergic signaling remodels BAT, inducing adaptive transcriptional changes that expand thermogenic capacity. Here, we show that the estrogen-related receptors alpha and gamma (ERRα, ERRγ) are collectively critical effectors of adrenergically stimulated transcriptional reprogramming of BAT. Mice lacking adipose ERRs (ERRαγAd−/−) have reduced oxidative and thermogenic capacity and rapidly become hypothermic when exposed to cold. ERRαγAd−/− mice treated long term with a β3-adrenergic agonist fail to expand oxidative or thermogenic capacity and do not increase energy expenditure in response to norepinephrine (NE). Furthermore, ERRαγAd−/− mice fed a high-fat diet do not lose weight or show improved glucose tolerance when dosed with β3-adrenergic agonists. The molecular basis of these defects is the finding that ERRs mediate the bulk of the transcriptional response to adrenergic stimulation. Adipose ERRs collectively control brown fat oxidative and thermogenic capacity Adipose ERRs are essential for BAT remodeling induced by β-adrenergic agonism ERRs control the bulk of the transcriptional response to adrenergic stimulation Mice that lack adipose ERRs show no metabolic benefits of β-adrenergic agonism Adrenergic Receptor Function; Biochemical Mechanism; Molecular Biology
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影响因子：
4.8
作者：
Gantner, Marin L.;Hazen, Bethany C.;Kralli, Anastasia
通讯作者：
Kralli, Anastasia
DOI：
10.1152/ajpendo.00009.2005
发表时间：
2005-10-01
影响因子：
5.1
作者：
Granneman, JG;Li, PP;Lu, YY
通讯作者：
Lu, YY
影响因子：
64.8
作者：
GIGUERE, V;YANG, N;EVANS, RM
通讯作者：
EVANS, RM
影响因子：
64.5
作者：
Bookout, Angie L.;Jeong, Yangsik;Mangelsdorf, David J.
通讯作者：
Mangelsdorf, David J.
影响因子：
29
作者：
Dufour, Catherine R.;Wilson, Brian J.;Giguere, Vincent
通讯作者：
Giguere, Vincent