Deletion of RNF186 Expression Suppresses Diet-induced Hepatic Steatosis by Regulating Insulin Activity

Overview

Journal iScience

Publisher Cell Press

Date 2022 Feb 24

PMID 35198905

Authors

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

Affiliations

Soon will be listed here.

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 ) 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.

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PMID: 38079053 DOI: 10.1007/s11596-023-2781-y.

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