Hepatic mTOR-AKT2-Insig2 signaling pathway contributes to the improvement of hepatic steatosis after Roux-en-Y Gastric Bypass in mice

Publication date: Available online 15 December 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Qinling Pan, Tingfeng Qin, Yuan Gao, Shaojian Li, Danjie Li, Miao Peng, Hening Zhai, Geyang XuAbstractRoux-en-Y Gastric Bypass (RYGB) remains one of the most effective options in treatment of non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanisms are not clear yet. Here, we evaluated the relationship among hepatic mechanistic target of rapamycin (mTOR)-AKT2-insulin-induced gene 2 (Insig2) signaling, lipogenic transcription factors and lipid synthesis enzymes in obese mice with or without RYGB operation. Hepatic mTOR activity and Insig2a were stimulated, while AKT2, sterol response element-binding protein 1c (SREBP1c), peroxisome proliferator-activated receptor γ (PPARγ), lipogenic genes such as acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) were decreased by Roux-en-Y Gastric Bypass in both DMSO and rapamycin treated diet-induced obese (DIO) mice. Increment of hepatic lipogenesis and decline of mTOR signaling induced by rapamycin were significantly reversed by RYGB in DIO mice. RYGB significantly improved high-fat diet- and rapamycin- induced hepatic steatosis by suppression of de novo lipogenesis. Administration of adenovirus-mediated p70 ribosomal protein subunit 6 kinase 1 (Ad-S6K1) from tail vein improved hepatic steatosis. Infusion of Ad-S6K1 suppressed AKT2, SREBP1c, PPARγ, and lipogenesis-related gen...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research