The hepatokine Tsukushi gates energy expenditure via brown fat sympathetic innervation
The hepatokine Tsukushi gates energy expenditure via brown fat sympathetic innervation
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DOI：
10.1038/s42255-018-0020-9
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发表时间：
2019-02-01
影响因子：
20.8
通讯作者：
Lin, Jiandie D.
中科院分区：
文献类型：
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作者：
Wang, Qiuyu;Sharma, Vishal P.;Lin, Jiandie D.
生热作用是全身能量消耗和代谢动态平衡的重要因素。虽然促进能量消耗的循环因素是已知的，但抑制能量消耗的内分泌分子在很大程度上仍然难以捉摸。在这里，我们发现筑地(TSK)是一种富含肝脏的分泌因子，在能量消耗增加时具有高度的诱导性。肥胖患者肝组织TSK表达和血浆TSK水平升高。在小鼠中，TSK缺乏增加了交感神经支配和脂肪组织中去甲肾上腺素的释放，导致肾上腺素能信号和产热作用增强，减轻棕色脂肪美白，并保护免受饮食诱导的肥胖。我们的数据揭示了TSK作为负反馈机制的一部分，该机制控制热能消耗，并强调TSK是代谢性疾病治疗干预的潜在目标。
Thermogenesis is an important contributor to whole-body energy expenditure and metabolic homeostasis. Although circulating factors that promote energy expenditure are known, endocrine molecules that suppress energy expenditure have remained largely elusive. Here we found that Tsukushi (TSK) is a liver-enriched secreted factor that is highly inducible in response to increased energy expenditure. Hepatic Tsk expression and plasma TSK levels were elevated in obesity. In mice, TSK deficiency increased sympathetic innervation and norepinephrine release in adipose tissue, leading to enhanced adrenergic signalling and thermogenesis, attenuation of brown fat whitening, and protection from diet-induced obesity. Our data reveal TSK as part of a negative feedback mechanism that gates thermogenic energy expenditure and highlights TSK as a potential target for therapeutic intervention in metabolic disease.