Adiponectin reduces thermogenesis by inhibiting brown adipose tissue activation in mice.

Adiponectin reduces thermogenesis by inhibiting brown adipose tissue activation in mice.
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DOI:
10.1007/s00125-014-3180-5
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发表时间:
2014-05
期刊:
影响因子:
8.2
通讯作者:
Shao, Jianhua
Shao, Jianhua
中科院分区:
医学1区
文献类型:
--
作者:
Qiao, Liping;Yoo, Hyung Sun;Bosco, Chris;Lee, Bonggi;Feng, Gen-Sheng;Schaack, Jerome;Chi, Nai-Wen;Shao, Jianhua

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脂联素是一种脂肪细胞源性激素,在能量平衡中起重要作用。本研究的主要目的是调查是否脂联素调节棕色脂肪组织(BAT)的激活和产热。在室温和冷暴露期间监测遗传小鼠模型的核心体温(CBTs)。采用体外培养的棕色脂肪细胞和病毒载体介导的基因转导方法,研究脂联素对Ucp 1基因表达的调控作用及其机制。脂联素敲除小鼠(Adipoq−/−)的CBT在室温和寒冷(4°C)挑战期间均显著高于野生型(WT)小鼠。相反,Adipoq−/−小鼠中脂联素的重建显著减弱β肾上腺素能受体激动剂诱导的肩胛间BAT产热。经过10天的间歇性冷暴露,Adipoq−/−小鼠表现出更高的UCP 1表达和腹股沟脂肪中更多的棕色样结构比WT小鼠。巧合的是,我们发现脂联素的抗生热作用不需要AdipoR 1和AdipoR 2这两种众所周知的脂联素受体。与脂联素的抗生热作用形成鲜明对比的是,AdipoR 1尤其是AdipoR 2促进BAT活化。脂联素通过抑制棕色脂肪细胞中β3-肾上腺素能受体的表达来抑制Ucp 1基因的表达。这项研究表明,脂联素抑制产热,这可能是脂联素减少能量消耗的机制。
Adiponectin is an adipocyte-derived hormone that plays an important role in energy homeostasis. The main objective of this study was to investigate whether or not adiponectin regulates brown adipose tissue (BAT) activation and thermogenesis. Core body temperatures (CBTs) of genetic mouse models were monitored at room temperature and during cold exposure. Cultured brown adipocytes and viral vector-mediated gene transduction were used to study the regulatory effects of adiponectin on Ucp1 gene expression and the underlying mechanisms. The CBTs of adiponectin knockout mice (Adipoq−/−) were significantly higher than those of wild type (WT) mice both at room temperature and during the cold (4°C) challenge. Conversely, reconstitution of adiponectin in Adipoq−/− mice significantly blunted β adrenergic receptor agonist-induced thermogenesis of interscapular BAT. After 10 days of intermittent cold exposure, Adipoq−/− mice exhibited higher UCP1 expression and more brown-like structure in inguinal fat than WT mice. Paradoxically, we found that the anti-thermogenic effect of adiponectin requires neither AdipoR1 nor AdipoR2, two well-known adiponectin receptors. In sharp contrast to the anti-thermogenic effects of adiponectin, AdipoR1 and especially AdipoR2 promote BAT activation. Mechanistically, adiponectin was found to inhibit Ucp1 gene expression by suppressing β3-adrenergic receptor expression in brown adipocytes. This study demonstrates that adiponectin suppresses thermogenesis, which is likely to be a mechanism whereby adiponectin reduces energy expenditure.
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