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
Affiliations
Xiuqi Hu
Department of Biochemistry and Molecular Biology, Metabolic Disease Research Center, School of Basic Medicine, Anhui Medical University, Hefei 230032, China
Qifan Zhang
Department of Biochemistry and Molecular Biology, Metabolic Disease Research Center, School of Basic Medicine, Anhui Medical University, Hefei 230032, China
Manyu Guo
Department of Biochemistry and Molecular Biology, Metabolic Disease Research Center, School of Basic Medicine, Anhui Medical University, Hefei 230032, China
Qianqian Yuan
Department of Biochemistry and Molecular Biology, Metabolic Disease Research Center, School of Basic Medicine, Anhui Medical University, Hefei 230032, China
Xin Tong
Department of Biochemistry and Molecular Biology, Metabolic Disease Research Center, School of Basic Medicine, Anhui Medical University, Hefei 230032, China
Qing Zhang
Department of Biochemistry and Molecular Biology, Metabolic Disease Research Center, School of Basic Medicine, Anhui Medical University, Hefei 230032, China
Li Lin
Department of Biochemistry and Molecular Biology, Metabolic Disease Research Center, School of Basic Medicine, Anhui Medical University, Hefei 230032, China
Lei Zhang
Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin 300070, China
Shujuan Lv
Department of Microbiology, School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China
Xiaojun Liu
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Science, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100005, China
Chaobing Gao
Department of Otorhinolaryngology Head and Neck, First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Corresponding author
Yongsheng Chang
Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin 300070, China; Corresponding author
Huabing Zhang
Department of Biochemistry and Molecular Biology, Metabolic Disease Research Center, School of Basic Medicine, Anhui Medical University, Hefei 230032, China; Corresponding author
Summary: 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 (RNF186LKO) 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.
