Huang Y, Yu F, Ding Y, et al, Hepatic IL22RA1 deficiency promotes hepatic steatosis by modulating oxysterol in the liver, Hepatology, 2024. (IF: 12.9)

Abstract: Hepatic IL22RA1 deficiency leads to the accumulation of specific oxidative sterols (3β HCA), which increases adipogenesis by activating the transcription factor 3/oxosterol 7α-hydroxylase axis. IL-22 treatment can reduce 3β HCA-induced adipogenesis, and restoration of oxidative sterol 7α-hydroxylase or silencing activates transcription factor 3 to reduce hepatic 3β HCA and lipid content. IL22RA1 maintain liver lipid homeostasis by activating the transcription factor 3/oxidative sterol 7α-hydroxylase pathway, 3β HCA is involved in liver lipid homeostasis, providing a new target for NAFLD treatment.

摘要：非酒精性脂肪肝病（NAFLD）由脂质代谢失衡引起，肝内调节脂质稳态的机制尚不清楚。肝脏中的IL22RA1对于调节肝脏脂质平衡至关重要。在NAFLD情况下，IL22RA1表达下调，导致肝脂肪变性和代谢问题。肝脏IL22RA1缺乏导致特定氧化固醇（3β HCA）积累，通过激活转录因子3/氧化固醇7α-羟化酶轴增加脂肪生成。IL-22治疗可以减少3β HCA诱导的脂肪生成，恢复氧化固醇7α-羟化酶或沉默激活转录因子3可降低肝脏3β HCA和脂质含量。IL22RA1通过激活转录因子3/氧化固醇7α-羟化酶途径维持肝脏脂质稳态，3β HCA与肝脏脂质平衡有关，为NAFLD治疗提供新靶点。