Rubicon deficiency exacerbates fasting-induced hepatic steatosis  

作　　者：Fan Dong Xiao-Wen Hu Shasha Zhang Fan He Amber Naz Lin He Hongxin Zhu 

机构地区：[1]Bio-X Institutes,Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders,Ministry of Education,Shanghai Jiao Tong University,Shanghai,China

出　　处：《Journal of Bio-X Research》2022年第1期35-41,共7页生物组学研究杂志（英文）

基　　金：This study was supported by the National Natural Science Foundation of China(Nos.81974024 and 82171567);the Shanghai Natural Science Foundation(No.16ZR1418200).

摘　　要：Objective: Rubicon is an inhibitory interacting protein of the autophagy-related protein Uvrag. We previously showed thatRubicon deficiency promotes autophagic fluxin vivo and that autophagy can degrade lipid droplets. This study aimed to investigate the effects of Rubicon deficiency on fasting-induced hepatic steatosis.Methods: Two-month-old wild-type (WT) andRubicon-deficient mice were subjected to feeding or fasting for 24 hours to induce hepatic steatosis. The distribution of liver lipid droplets was revealed by oil red O staining. Hepatic and plasma triglyceride, non-esterified fatty acid (NEFA), and cholesterol levels were detected using commercially available kits. Real-time reverse transcriptasepolymerase chain reaction was performed to analyze the mRNA expression of genes related to lipid metabolism in the liver. Western blot was conducted to assess autophagy-related protein levels in the liver. The animal experiments were approved by the Institutional Animal Care and Use Committee at Shanghai Jiao Tong University, China.Results: We showed that under fasting conditions,Rubicon-deficient mice had more lipid droplets in the liver than WT controls. Consistent with these results, the hepatic triglyceride, NEFA, and cholesterol levels in fastedRubicon-deficient mice were significantly higher than those of fasted WT controls. The levels ofSREBP-1, a key regulator of lipid synthesis, were significantly lower in livers from fasted WT mice than those of fed WT mice. However, the decrease inSREBP-1 in fasted mice was attenuated byRubicon deficiency. Western blot analysis demonstrated that the fasting-induced increase in autophagic flux was amplified byRubicon deficiency. Finally, we showed thatRubicon deficiency in mice led to elevated plasma triglyceride and NEFA acid levels under fasting conditions.Conclusion: Rubicon deficiency exacerbates fasting-induced hepatic steatosis in mice.

关 键 词：AUTOPHAGY FASTING hepatic steatosis LIVER RUBICON 

分 类 号：R575.5[医药卫生—消化系统]