QKI regulates adipose tissue metabolism by acting as a brake on thermogenesis and promoting obesity. (23rd December 2019)

• Record Type: Journal Article
• Authors: Lu, Huanyu; Ye, Zichen; Zhai, Yue; Wang, Li; Liu, Ying; Wang, Jiye; Zhang, Wenbin; Luo, Wenjing; Lu, Zifan; Chen, Jingyuan
• Is Part Of: EMBO reports. Volume 21:Number 1(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-12-23
• Subjects: adipose -- obesity -- posttranscriptional regulation -- QKI -- thermogenesis; Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.201947929
• Languages: English
• ISSNs: 1469-221X

Abstract

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 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. Synopsis: RNA binding protein QKI is induced by cold stimulus and impedes thermogenesis by repressing translation of thermogenesis regulators such as UCP1 and PGC1α. QKI deficient mice are protected from high fat diet induced obesity and insulin resistance. QKI deficiency promotes adipose thermogenesis and prevents cold induced hypothermia. QKI binds mRNAs encoding UCP1 and PGC1α and decreases their stability, nuclear export and translational efficiency. cAMP/CREB signaling transcriptionally upregulates QKI, which in turn represses thermogenesis. Abstract : RNA binding protein QKI is induced by cold stimulus and impedes thermogenesis by repressing translation of thermogenesis regulators such as UCP1 and PGC1α.