首页|The critical role of BTRC in hepatic steatosis as an ATGL E3 ligase

The critical role of BTRC in hepatic steatosis as an ATGL E3 ligase

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Non-alcoholic fatty liver disease(NAFLD),characterized by hepatic steatosis,is one of the commonest causes of liver dysfunction.Adipose triglyceride lipase(ATGL)is closely related to lipid turnover and hepatic steatosis as the speed-limited triacylglycerol lipase in liver lipolysis.However,the expression and regulation of ATGL in NAFLD remain unclear.Herein,our results showed that ATGL protein levels were decreased in the liver tissues of high-fat diet(HFD)-fed mice,naturally obese mice,and cholangioma/hepatic carcinoma patients with hepatic steatosis,as well as in the oleic acid-induced hepatic steatosis cell model,while ATGL mRNA levels were not changed.ATGL protein was mainly degraded through the proteasome pathway in hepatocytes.Beta-transducin repeat containing(BTRC)was upregulated and negatively correlated with the decreased ATGL level in these hepatic steatosis models.Consequently,BTRC was identified as the E3 ligase for ATGL through predominant ubiquitination at the lysine 135 residue.Moreover,adenovirus-mediated knockdown of BTRC ameliorated steatosis in HFD-fed mouse livers and oleic acid-treated liver cells via upregulating the ATGL level.Taken together,BTRC plays a crucial role in hepatic steatosis as a new ATGL E3 ligase and may serve as a potential therapeutic target for treating NAFLD.

adipose triglyceride lipase(ATGL)beta-transducin repeat containing(BTRC)non-alcoholic fatty liver disease(NAFLD)obesityproteasomal degradation

Weiwei Qi、Zhenzhen Fang、Chuanghua Luo、Honghai Hong、Yanlan Long、Zhiyu Dai、Junxi Liu、Yongcheng Zeng、Ti Zhou、Yong Xia、Xia Yang、Guoquan Gao

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Department of Biochemistry,Zhongshan School of Medicine,Sun Yat-sen University,Guangzhou 510080,China

Department of Clinical Laboratory,The Third Affiliated Hospital of Guangzhou Medical University,Guangzhou 510006,China

Department of Internal Medicine,University of Arizona College of Medicine,Phoenix,AZ 85004,USA

Guangdong Engineering&Technology Research Center for Gene Manipulation and Biomacromolecular Products,Sun Yat-sen University,Guangzhou 510080,China

Guangdong Province Key Laboratory of Brain Function and Disease,Zhongshan School of Medicine,Sun Yat-sen University,Guangzhou 510080,China

Key Laboratory of Tropical Disease Control,Ministry of Education,Sun Yat-sen University,Guangzhou 510080,China

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National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Key R&D Program of ChinaGuangdong Special Support Program for Young Top ScientistGuangdong Natural Science FundGuangdong Natural Science FundGuangdong Natural Science FundGuangdong Natural Science FundKey Sci-Tech Research Project of Guangzhou MunicipalityChina Postdoctoral Science FoundationChina Postdoctoral Science Foundation

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2023

10.1093/jmcb/mjad064

分子细胞生物学报(英文版)
中国科学院上海生命科学研究院,生物化学与细胞生物学研究所,中国细胞生物学学会

分子细胞生物学报(英文版)

CSTPCDCSCD
影响因子：0.595
ISSN：1673-520X
年,卷(期)：2023.(10)
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