Deletion of RNF186 expression suppresses diet-induced hepatic steatosis by regulating insulin activity

Xiuqi Hu; Qifan Zhang; Manyu Guo; Qianqian Yuan; Xin Tong; Qing Zhang; Li Lin; Lei Zhang; Shujuan Lv; Xiaojun Liu; Chaobing Gao; Yongsheng Chang; Huabing Zhang

doi:10.1016/j.isci.2022.103859

Deletion of RNF186 expression suppresses diet-induced hepatic steatosis by regulating insulin activity

iScience. 2022 Feb 2;25(2):103859. doi: 10.1016/j.isci.2022.103859. eCollection 2022 Feb 18.

Authors

Xiuqi Hu¹, Qifan Zhang¹, Manyu Guo¹, Qianqian Yuan¹, Xin Tong¹, Qing Zhang¹, Li Lin¹, Lei Zhang², Shujuan Lv³, Xiaojun Liu⁴, Chaobing Gao⁵, Yongsheng Chang², Huabing Zhang¹

Affiliations

¹ Department of Biochemistry and Molecular Biology, Metabolic Disease Research Center, School of Basic Medicine, Anhui Medical University, Hefei 230032, China.
² Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin 300070, China.
³ Department of Microbiology, School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China.
⁴ National Laboratory of Medical Molecular Biology, Institute of Basic Medical Science, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100005, China.
⁵ Department of Otorhinolaryngology Head and Neck, First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.

Abstract

RING finger protein186 (RNF186) is dramatically upregulated in steatotic livers. The physiological role of RNF186 in non-alcoholic fatty liver disease (NAFLD) remains obscure. Here, we found that hepatocyte-specific RNF186 knockout (RNF186 ^LKO ) mice were protected from HFD-induced obesity. RNF186 ablation in liver suppressed inflammatory responses and ER stress and alleviated insulin tolerance, leading to improved glucose and lipid metabolism under HFD conditions. RNA-seq and western blot analyses revealed a significant downregulation of peroxisome proliferator-activated receptor γ, stearoyl-CoA desaturase 1, and cluster of differentiation 36 in the liver of RNF186 knockout mice consuming HFD. RNF186 deletion in liver results in less weight gain during HFD feeding and is associated with reduced liver fat, inflammation, and improved glucose and insulin tolerance. In contrast, upregulation of RNF186 in C57BL/6J mice livers impaired lipid metabolism and insulin tolerance. The collective results suggest that RNF186 may be a potential regulator of NAFLD in obesity.

Keywords: Inflammation; Insulin resistance; Lipid metabolism; NAFLD; RNF186.