QKI regulates adipose tissue metabolism by acting as a brake on thermogenesis and promoting obesity
QKI regulates adipose tissue metabolism by acting as a brake on thermogenesis and promoting obesity
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QKI 通过抑制产热和促进肥胖来调节脂肪组织代谢
DOI：
10.15252/embr.201947929
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发表时间：
2019-12-23
期刊：
影响因子：
7.7
通讯作者：
Chen, Jingyuan
中科院分区：
文献类型：
--
作者：
Lu, Huanyu;Ye, Zichen;Chen, Jingyuan
脂肪组织控制着许多生理过程，其功能障碍在全身代谢紊乱的发展中具有致病作用。转录后调节在脂肪代谢中的作用尚未完全了解。在这里，我们证明RNA结合蛋白震颤（QKI）在控制脂肪组织的代谢稳态中发挥着重要作用。 QKI 缺陷小鼠对高脂饮食 (HFD) 引起的肥胖具有抵抗力。此外，QKI 消耗增加了棕色脂肪的能量耗散和皮下白色脂肪的褐变。小鼠脂肪组织特异性消耗 QKI 会增强冷诱导的生热作用，从而防止因冷刺激而出现体温过低。进一步的机制分析表明，QKI 是由 cAMP-cAMP 反应元件结合蛋白 (CREB) 轴转录诱导的，并通过降低编码 UCP1 和 PGC1α 的 mRNA 的稳定性、核输出和翻译来限制脂肪组织能量消耗。这些发现扩展了我们对转录后调节在脂肪代谢稳态中重要性的认识，并为预防肥胖及其相关代谢疾病提供了潜在的治疗靶点。
Adipose tissue controls numerous physiological processes, and its dysfunction has a causative role in the development of systemic metabolic disorders. The role of posttranscriptional regulation in adipose metabolism has yet to be fully understood. Here, we show that the RNA‐binding protein quaking (QKI) plays an important role in controlling metabolic homeostasis of the adipose tissue. QKI‐deficient mice are resistant to high‐fat‐diet (HFD)‐induced obesity. Additionally, QKI depletion increased brown fat energy dissipation and browning of subcutaneous white fat. Adipose tissue‐specific depletion of QKI in mice enhances cold‐induced thermogenesis, thereby preventing hypothermia in response to cold stimulus. Further mechanistic analysis reveals that QKI is transcriptionally induced by the cAMP‐cAMP response element‐binding protein (CREB) axis and restricts adipose tissue energy consumption by decreasing stability, nuclear export, and translation of mRNAs encoding UCP1 and PGC1α. These findings extend our knowledge of the significance of posttranscriptional regulation in adipose metabolic homeostasis and provide a potential therapeutic target to defend against obesity and its related metabolic diseases.