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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.<\/jats:p>","DOI":"10.1093\/jmcb\/mjad064","type":"journal-article","created":{"date-parts":[[2023,10,20]],"date-time":"2023-10-20T08:45:34Z","timestamp":1697791534000},"source":"Crossref","is-referenced-by-count":9,"title":["The critical role of BTRC in hepatic steatosis as an ATGL E3 ligase"],"prefix":"10.1093","volume":"15","author":[{"given":"Weiwei","family":"Qi","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou 510080 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenzhen","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou 510080 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanghua","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou 510080 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honghai","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou 510080 , China"},{"name":"Department of Clinical Laboratory, The Third Affiliated Hospital of Guangzhou Medical University , Guangzhou 510006 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanlan","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou 510080 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyu","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Arizona College of Medicine , Phoenix, AZ 85004 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junxi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou 510080 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongcheng","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou 510080 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8517-5405","authenticated-orcid":false,"given":"Ti","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou 510080 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Third Affiliated Hospital of Guangzhou Medical University , Guangzhou 510006 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou 510080 , China"},{"name":"Guangdong Engineering & Technology Research Center for Gene Manipulation and Biomacromolecular Products, Sun Yat-sen University , Guangzhou 510080 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8996-1470","authenticated-orcid":false,"given":"Guoquan","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou 510080 , China"},{"name":"Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou 510080 , China"},{"name":"Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University , Guangzhou 510080 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,10,23]]},"reference":[{"key":"2024062808333135500_bib1","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.freeradbiomed.2022.06.226","article-title":"Nonalcoholic steatohepatitis and mechanisms by which it is ameliorated by activation of the CNC-bZIP transcription factor Nrf2","volume":"188","author":"Bathish","year":"2022","journal-title":"Free Radic. 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