BTRC作为ATGL E3连接酶在肝脂肪变性中的关键作用。

IF 5.3 2区 生物学 Q2 CELL BIOLOGY
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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引用次数: 0

摘要

以肝脂肪变性为特征的非酒精性脂肪肝(NAFLD)是肝功能障碍的最常见原因之一。脂肪甘油三酯脂酶(ATGL)作为肝脏脂解中限速的三酰甘油脂酶,与脂质周转和肝脏脂肪变性密切相关。然而,ATGL在NAFLD中的表达和调节仍不清楚。在此,我们的研究结果表明,在高脂肪饮食(HFD)喂养的小鼠、自然肥胖小鼠、患有肝脂肪变性的胆管瘤/肝癌患者的肝组织中,以及在油酸诱导的肝脂肪变性细胞模型中,ATGL蛋白水平降低,而ATGL mRNA水平没有改变。ATGL蛋白在肝细胞中主要通过蛋白酶体途径降解。在这些肝脂肪变性模型中,β-转导素重复序列(BTRC)上调,并与ATGL水平下降呈负相关。因此,BTRC通过赖氨酸135残基的主要泛素化被鉴定为ATGL的E3连接酶。此外,腺病毒介导的BTRC敲低通过上调ATGL水平改善了HFD喂养的小鼠肝脏和油酸处理的肝细胞中的脂肪变性。总之,BTRC作为一种新的ATGL E3连接酶在肝脂肪变性中起着至关重要的作用,并可能成为治疗NAFLD的潜在治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The critical role of BTRC in hepatic steatosis as an ATGL E3 ligase.

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.

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来源期刊
CiteScore
9.60
自引率
1.80%
发文量
1383
期刊介绍: The Journal of Molecular Cell Biology ( JMCB ) is a full open access, peer-reviewed online journal interested in inter-disciplinary studies at the cross-sections between molecular and cell biology as well as other disciplines of life sciences. The broad scope of JMCB reflects the merging of these life science disciplines such as stem cell research, signaling, genetics, epigenetics, genomics, development, immunology, cancer biology, molecular pathogenesis, neuroscience, and systems biology. The journal will publish primary research papers with findings of unusual significance and broad scientific interest. Review articles, letters and commentary on timely issues are also welcome. JMCB features an outstanding Editorial Board, which will serve as scientific advisors to the journal and provide strategic guidance for the development of the journal. By selecting only the best papers for publication, JMCB will provide a first rate publishing forum for scientists all over the world.
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