GP73 is a TBC-domain Rab GTPase-activating protein contributing to the pathogenesis of non-alcoholic fatty liver disease without obesity.
GP73 is a TBC-domain Rab GTPase-activating protein contributing to the pathogenesis of non-alcoholic fatty liver disease without obesity.
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GP73 是一种 TBC 结构域 Rab GTP 酶激活蛋白，有助于非肥胖性非酒精性脂肪肝的发病机制。
DOI：
10.1038/s41467-021-27309-1
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发表时间：
2021-12-01
影响因子：
16.6
通讯作者：
Wei C
中科院分区：
文献类型：
--
作者：
Peng Y;Zeng Q;Wan L;Ma E;Li H;Yang X;Zhang Y;Huang L;Lin H;Feng J;Xu Y;Li J;Liu M;Liu J;Lin C;Sun Z;Cheng G;Zhang X;Liu J;Li D;Wei M;Mo Y;Mu X;Deng X;Zhang D;Dong S;Huang H;Fang Y;Gao Q;Yang X;Wu F;Zhong H;Wei C
非肥胖性非酒精性脂肪性肝病（NAFLD）的患病率在全球范围内不断增加，其病因和发病机制尚不清楚。在这里，我们显示GP 73，一种在各种肝病患者肝脏中上调的高尔基体蛋白，表现出Rab GTP酶激活蛋白（GAP）调节ApoB输出的活性。在常规饮食喂养后，肝脏-GP 73-高小鼠显示非肥胖NAFLD表型，其特征在于体重减轻、肝内脂质积累和逐渐的胰岛素抵抗发展，其中没有一个可以在肝脏-GAP失活的GP 73-高小鼠中重现。揭示了与GP 73诱导的非肥胖NAFLD和高脂饮食（HFD）诱导的肥胖NAFLD相关的共同和特异性基因表达特征。值得注意的是，二甲双胍使GP 73差距活性失活并使GP 73诱导的非肥胖NAFLD消退。GP 73在没有肥胖的NAFLD个体中病理性升高，并且GP 73阻断改善非肥胖NAFLD小鼠模型中的全身代谢。这些发现揭示了GP 73在触发非肥胖NAFLD中的病理生理作用，并可能为临床干预提供机会。脂质代谢和转运的失调有助于非酒精性脂肪性肝病（NAFLD）的发病机制。在这里，作者将GP 73鉴定为TBC结构域Rab GTP酶激活蛋白，其调节极低密度脂蛋白输出并促进小鼠的NAFLD发展。
The prevalence of non-obese nonalcoholic fatty liver disease (NAFLD) is increasing worldwide with unclear etiology and pathogenesis. Here, we show GP73, a Golgi protein upregulated in livers from patients with a variety of liver diseases, exhibits Rab GTPase-activating protein (GAP) activity regulating ApoB export. Upon regular-diet feeding, liver-GP73-high mice display non-obese NAFLD phenotype, characterized by reduced body weight, intrahepatic lipid accumulation, and gradual insulin resistance development, none of which can be recapitulated in liver-GAP inactive GP73-high mice. Common and specific gene expression signatures associated with GP73-induced non-obese NAFLD and high-fat diet (HFD)-induced obese NAFLD are revealed. Notably, metformin inactivates the GAP activity of GP73 and alleviates GP73-induced non-obese NAFLD. GP73 is pathologically elevated in NAFLD individuals without obesity, and GP73 blockade improves whole-body metabolism in non-obese NAFLD mouse model. These findings reveal a pathophysiological role of GP73 in triggering non-obese NAFLD and may offer an opportunity for clinical intervention. Dysregulation of lipid metabolism and transport contribute to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Here the authors identify GP73 as a TBC-domain Rab GTPase-activating protein that regulates very low-density lipoprotein export and promotes NAFLD development in mice.
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影响因子：
16.6
作者：
Lee G;You HJ;Bajaj JS;Joo SK;Yu J;Park S;Kang H;Park JH;Kim JH;Lee DH;Lee S;Kim W;Ko G
通讯作者：
Ko G
RAB GTPases在膜交通和细胞生理学中的作用。
影响因子：
33.6
作者：
Hutagalung AH;Novick PJ
通讯作者：
Novick PJ
影响因子：
3.9
作者：
Gibbons, GF;Wiggins, D;Hebbachi, AM
通讯作者：
Hebbachi, AM
影响因子：
13.5
作者：
Fujita, Koji;Nozaki, Yuichi;Nakajima, Atsushi
通讯作者：
Nakajima, Atsushi
影响因子：
2.9
作者：
Cerqueira, Nuno M. F. S. A.;Oliveira, Eduardo F.;Fernandes, P. A.
通讯作者：
Fernandes, P. A.