PMID- 30562559
OWN - NLM
STAT- MEDLINE
DCOM- 20191031
LR  - 20211204
IS  - 1879-260X (Electronic)
IS  - 0925-4439 (Linking)
VI  - 1865
IP  - 3
DP  - 2019 Mar 1
TI  - Hepatic mTOR-AKT2-Insig2 signaling pathway contributes to the improvement of 
      hepatic steatosis after Roux-en-Y Gastric Bypass in mice.
PG  - 525-534
LID - S0925-4439(18)30500-3 [pii]
LID - 10.1016/j.bbadis.2018.12.014 [doi]
AB  - Roux-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 gamma (PPARgamma), 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, PPARgamma, and 
      lipogenesis-related genes while stimulating Insig2a in DIO mice. Ad-S6K1 
      decreased oleic acid-induced lipid deposition in primary mouse hepatocytes. Our 
      results suggest that mTOR-AKT2-Insig2 signaling pathway contributes to the 
      improvement effect of RYGB on hepatic steatosis induced by high-fat diet.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Pan, Qinling
AU  - Pan Q
AD  - Department of Physiology, School of Medicine, Jinan University, 601 Huangpu 
      Avenue West, Tianhe District, Guangzhou, Guangdong 510632, China.
FAU - Qin, Tingfeng
AU  - Qin T
AD  - Department of Physiology, School of Medicine, Jinan University, 601 Huangpu 
      Avenue West, Tianhe District, Guangzhou, Guangdong 510632, China.
FAU - Gao, Yuan
AU  - Gao Y
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Peking University, Beijing 100191, China.
FAU - Li, Shaojian
AU  - Li S
AD  - Department of Physiology, School of Medicine, Jinan University, 601 Huangpu 
      Avenue West, Tianhe District, Guangzhou, Guangdong 510632, China.
FAU - Li, Danjie
AU  - Li D
AD  - Department of Physiology, School of Medicine, Jinan University, 601 Huangpu 
      Avenue West, Tianhe District, Guangzhou, Guangdong 510632, China.
FAU - Peng, Miao
AU  - Peng M
AD  - Department of Physiology, School of Medicine, Jinan University, 601 Huangpu 
      Avenue West, Tianhe District, Guangzhou, Guangdong 510632, China.
FAU - Zhai, Hening
AU  - Zhai H
AD  - Endoscopy Center, The First Affiliated Hospital of Jinan University, 613 Huangpu 
      Avenue West, Tianhe District, Guangzhou, Guangdong 510630, China.
FAU - Xu, Geyang
AU  - Xu G
AD  - Department of Physiology, School of Medicine, Jinan University, 601 Huangpu 
      Avenue West, Tianhe District, Guangzhou, Guangdong 510632, China. Electronic 
      address: xugeyangliang@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181215
PL  - Netherlands
TA  - Biochim Biophys Acta Mol Basis Dis
JT  - Biochimica et biophysica acta. Molecular basis of disease
JID - 101731730
RN  - 0 (Insig2 protein, mouse)
RN  - 0 (Membrane Proteins)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Akt2 protein, mouse)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Diet, High-Fat
MH  - Fatty Liver/etiology/metabolism/pathology/*surgery
MH  - *Gastric Bypass/rehabilitation
MH  - Lipogenesis/genetics/*physiology
MH  - Liver/*metabolism
MH  - Male
MH  - Membrane Proteins/genetics/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Obese
MH  - Obesity/etiology/metabolism/pathology/surgery
MH  - Proto-Oncogene Proteins c-akt/genetics/*metabolism
MH  - Signal Transduction/genetics
MH  - TOR Serine-Threonine Kinases/genetics/*metabolism
OTO - NOTNLM
OT  - AKT2
OT  - Hepatic lipogenesis
OT  - Insig2
OT  - RYGB
OT  - mTOR
EDAT- 2018/12/19 06:00
MHDA- 2019/11/02 06:00
CRDT- 2018/12/19 06:00
PHST- 2018/08/10 00:00 [received]
PHST- 2018/11/26 00:00 [revised]
PHST- 2018/12/12 00:00 [accepted]
PHST- 2018/12/19 06:00 [pubmed]
PHST- 2019/11/02 06:00 [medline]
PHST- 2018/12/19 06:00 [entrez]
AID - S0925-4439(18)30500-3 [pii]
AID - 10.1016/j.bbadis.2018.12.014 [doi]
PST - ppublish
SO  - Biochim Biophys Acta Mol Basis Dis. 2019 Mar 1;1865(3):525-534. doi: 
      10.1016/j.bbadis.2018.12.014. Epub 2018 Dec 15.