PMID- 37451514
OWN - NLM
STAT- Publisher
LR  - 20230804
IS  - 1665-2681 (Print)
IS  - 1665-2681 (Linking)
VI  - 28
IP  - 6
DP  - 2023 Jul 12
TI  - Metformin ameliorates liver fibrosis induced by congestive hepatopathy via the 
      mTOR/HIF-1alpha signaling pathway.
PG  - 101135
LID - S1665-2681(23)00239-9 [pii]
LID - 10.1016/j.aohep.2023.101135 [doi]
AB  - INTRODUCTION AND OBJECTIVES: Congestive hepatopathy (CH) is a hepatic vascular 
      disease that results in chronic liver congestion, which can lead to liver 
      fibrosis. New uses of metformin have been discovered over the years. However, the 
      function of metformin in congestive liver fibrosis is not yet fully understood. 
      This study aimed to investigate the effect of metformin on liver fibrosis in a 
      mouse model of CH. MATERIALS AND METHODS: Partial ligation of the inferior vena 
      cava (pIVCL) was used to establish a mouse model of liver congestion. Metformin 
      (0.1%) was added to the daily drinking water of the animals, and the effect of 
      metformin on liver tissue was studied after 6 weeks. Hepatic stellate cells 
      (HSCs) were also stimulated with CoCl(2) to investigate the inhibitory impact of 
      metformin on the mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1alpha 
      (HIF-1alpha) pathway. RESULTS: Metformin attenuated liver congestion; decreased the 
      expression of collagen, fibronectin, alpha-smooth muscle actin (alpha-SMA), and HIF-1alpha; 
      and ameliorated liver fibrosis in pIVCL mice. The proliferation and migration of 
      HSCs were inhibited by metformin in vitro, which prevented alpha-SMA expression and 
      restrained HSC activation. The expression levels of phosphorylated-mTOR, HIF-1alpha, 
      and vascular endothelial growth factor were also decreased. CONCLUSIONS: 
      Metformin inhibits CH-induced liver fibrosis. Functionally, this beneficial 
      effect may be the result of inhibition of HSC activation and of the mTOR/HIF-1alpha 
      signaling pathway.
CI  - Copyright (c) 2023 Fundacion Clinica Medica Sur, A.C. Published by Elsevier Espana, 
      S.L.U. All rights reserved.
FAU - Yang, Jing
AU  - Yang J
AD  - Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of 
      Zhengzhou University, Zhengzhou, Henan, 450052, China.
FAU - Li, Suxin
AU  - Li S
AD  - Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of 
      Zhengzhou University, Zhengzhou, Henan, 450052, China.
FAU - Liu, Shengyan
AU  - Liu S
AD  - Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of 
      Zhengzhou University, Zhengzhou, Henan, 450052, China.
FAU - Zhang, Yuehui
AU  - Zhang Y
AD  - Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of 
      Zhengzhou University, Zhengzhou, Henan, 450052, China.
FAU - Shen, Dongqi
AU  - Shen D
AD  - Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of 
      Zhengzhou University, Zhengzhou, Henan, 450052, China.
FAU - Wang, Peiju
AU  - Wang P
AD  - Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of 
      Zhengzhou University, Zhengzhou, Henan, 450052, China.
FAU - Dang, Xiaowei
AU  - Dang X
AD  - Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of 
      Zhengzhou University, Zhengzhou, Henan, 450052, China. Electronic address: 
      dangxw1001@zzu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20230712
PL  - Mexico
TA  - Ann Hepatol
JT  - Annals of hepatology
JID - 101155885
SB  - IM
OTO - NOTNLM
OT  - HIF-1alpha, mTOR
OT  - congestive hepatopathy
OT  - liver fibrosis
OT  - metformin
COIS- Declaration of interests None.
EDAT- 2023/07/15 10:42
MHDA- 2023/07/15 10:42
CRDT- 2023/07/14 19:26
PHST- 2023/03/24 00:00 [received]
PHST- 2023/05/22 00:00 [revised]
PHST- 2023/06/05 00:00 [accepted]
PHST- 2023/07/15 10:42 [pubmed]
PHST- 2023/07/15 10:42 [medline]
PHST- 2023/07/14 19:26 [entrez]
AID - S1665-2681(23)00239-9 [pii]
AID - 10.1016/j.aohep.2023.101135 [doi]
PST - aheadofprint
SO  - Ann Hepatol. 2023 Jul 12;28(6):101135. doi: 10.1016/j.aohep.2023.101135.