Dataset Information

QKI regulates adipose tissue metabolism by acting as a brake on thermogenesis and promoting obesity.

ABSTRACT: 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 PGC1?. 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.

SUBMITTER: Lu H

PROVIDER: S-EPMC6944952 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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QKI regulates adipose tissue metabolism by acting as a brake on thermogenesis and promoting obesity.

Lu Huanyu H Ye Zichen Z Zhai Yue Y Wang Li L Liu Ying Y Wang Jiye J Zhang Wenbin W Luo Wenjing W Lu Zifan Z Chen Jingyuan J

EMBO reports 20191223 1

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 ...[more]

PMID: 31868295

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Project description:Obesity occurs when excess energy accumulates in white adipose tissue (WAT), whereas brown adipose tissue (BAT), which is specialized in dissipating energy through thermogenesis, potently counteracts obesity. White adipocytes can be converted to thermogenic "brown-like" cells (beige cells; WAT browning) under various stimuli, such as cold exposure. AMP-activated protein kinase (AMPK) is a crucial energy sensor that regulates energy metabolism in multiple tissues. However, the role of AMPK in adipose tissue function, especially in the WAT browning process, is not fully understood. To illuminate the effect of adipocyte AMPK on energy metabolism, we generated Adiponectin-Cre-driven adipose tissue-specific AMPK ?1/?2 KO mice (AKO). These AKO mice were cold intolerant and their inguinal WAT displayed impaired mitochondrial integrity and biogenesis, and reduced expression of thermogenic markers upon cold exposure. High-fat-diet (HFD)-fed AKO mice exhibited increased adiposity and exacerbated hepatic steatosis and fibrosis and impaired glucose tolerance and insulin sensitivity. Meanwhile, energy expenditure and oxygen consumption were markedly decreased in the AKO mice both in basal conditions and after stimulation with a ?3-adrenergic receptor agonist, CL 316,243. In contrast, we found that in HFD-fed obese mouse model, chronic AMPK activation by A-769662 protected against obesity and related metabolic dysfunction. A-769662 alleviated HFD-induced glucose intolerance and reduced body weight gain and WAT expansion. Notably, A-769662 increased energy expenditure and cold tolerance in HFD-fed mice. A-769662 treatment also induced the browning process in the inguinal fat depot of HFD-fed mice. Likewise, A-769662 enhanced thermogenesis in differentiated inguinal stromal vascular fraction (SVF) cells via AMPK signaling pathway. In summary, a lack of adipocyte AMPK? induced thermogenic impairment and obesity in response to cold and nutrient-overload, respectively, whereas chronic AMPK activation by A-769662 promoted WAT browning in inguinal WAT and protected against HFD-induced obesity and related metabolic dysfunction. These findings reveal a vital role for adipocyte AMPK in regulating the browning process in inguinal WAT and in maintaining energy homeostasis, which suggests that the targeted activation of adipocyte AMPK may be a promising strategy for anti-obesity therapy.

Dataset Information

QKI regulates adipose tissue metabolism by acting as a brake on thermogenesis and promoting obesity.

Publications

QKI regulates adipose tissue metabolism by acting as a brake on thermogenesis and promoting obesity.

Similar Datasets

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