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.

中文翻译：

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QKI通过阻止生热并促进肥胖来调节脂肪组织的代谢。

脂肪组织控制着许多生理过程，其功能障碍在全身性代谢疾病的发展中起着致病作用。转录后调控在脂肪代谢中的作用尚未完全了解。在这里，我们表明RNA结合蛋白的地震（QKI）在控制脂肪组织的代谢稳态方面起着重要的作用。QKI缺陷小鼠对高脂饮食（HFD）诱导的肥胖具有抵抗力。此外，QKI消耗增加了褐色脂肪的能量耗散和皮下白色脂肪的褐变。小鼠QKI的脂肪组织特异性消耗增强了冷诱导的生热作用，从而防止了冷刺激引起的体温过低。进一步的机理分析表明，QKI由cAMP-cAMP反应元件结合蛋白（CREB）轴转录诱导，并通过降低稳定性，核输出以及编码UCP1和PGC1α的mRNA的翻译来限制脂肪组织的能量消耗。这些发现扩展了我们对转录后调控在脂肪代谢稳态中的重要性的认识，并为防御肥胖症及其相关的代谢性疾病提供了潜在的治疗靶标。