Multiple omics study identifies an interspecies conserved driver for nonalcoholic steatohepatitis

Authors: Xiao‐Jing Zhang, Zhi‐Gang She, Junyong Wang, Dating Sun, Lijun Shen, Hui Xiang, Xu Cheng, Yan‐Xiao Ji, Yongping Huang, Penglong Li, Xia Yang, Yanjie Cheng, Junpeng Ma, Haiping Wang, Yufeng Hu, Fengjiao Hu, Song Tian, Han Tian, Peng Zhang, Guang‐Nian Zhao, Lin Wang, Manli Hu, Qin Yang, Lihua Zhu, Jingjing Cai, Juan Yang, Xin Zhang, Xinliang Ma, Qingbo Xu, Rhian M. Touyz, Peter P. Liu, Rohit Loomba, Yibin Wang, Hongliang Li - Science Translational Medicine 2021 cited by 47

) gene, was closely correlated with NASH severity in humans, macaques with spontaneously developed NASH, as well as swine and mouse dietary NASH models. Using gain- and loss-of-function studies, we found that ALOX12 markedly exacerbated NASH in both mice and Bama pig models. ALOX12 was shown to induce NASH by directly targeting acetyl-CoA carboxylase 1 (ACC1) via a lysosomal degradation mechanism. Overall, our findings reveal a key molecular driver of NASH pathogenesis and suggest that ALOX12-ACC1 interaction may be a therapeutic target in NASH.