PMID- 34065108
OWN - NLM
STAT- MEDLINE
DCOM- 20210628
LR  - 20210914
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 9
DP  - 2021 May 9
TI  - Metformin Actions on the Liver: Protection Mechanisms Emerging in Hepatocytes and 
      Immune Cells against NASH-Related HCC.
LID - 10.3390/ijms22095016 [doi]
LID - 5016
AB  - Nonalcoholic fatty liver disease (NAFLD) is strongly linked to the global 
      epidemic of obesity and type 2 diabetes mellitus (T2DM). Notably, NAFLD can 
      progress from the mildest form of simple steatosis to nonalcoholic 
      steatohepatitis (NASH) that increases the risk for hepatocellular carcinoma 
      (HCC), which is a malignancy with a dismal prognosis and rising incidence in the 
      United States and other developed counties, possibly due to the epidemic of 
      NAFLD. Metformin, the first-line drug for T2DM, has been suggested to reduce 
      risks for several types of cancers including HCC and protect against NASH-related 
      HCC, as revealed by epidemical studies on humans and preclinical studies on 
      animal models. This review focuses on the pathogenesis of NASH-related HCC and 
      the mechanisms by which metformin inhibits the initiation and progression of 
      NASH-related HCC. Since the functional role of immune cells in liver homeostasis 
      and pathogenesis is increasingly appreciated in developing anti-cancer therapies 
      on liver malignancies, we discuss both the traditional targets of metformin in 
      hepatocytes and the recently defined effects of metformin on immune cells.
FAU - Zhang, Yueqi
AU  - Zhang Y
AUID- ORCID: 0000-0002-1189-2118
AD  - Cell and Molecular Biology Program, College of Natural Science, Michigan State 
      University, East Lansing, MI 48824, USA.
AD  - Department of Physiology, College of Natural Science, Michigan State University, 
      East Lansing, MI 48824, USA.
FAU - Wang, Hongbing
AU  - Wang H
AD  - Department of Physiology, College of Natural Science, Michigan State University, 
      East Lansing, MI 48824, USA.
FAU - Xiao, Hua
AU  - Xiao H
AD  - Department of Physiology, College of Natural Science, Michigan State University, 
      East Lansing, MI 48824, USA.
LA  - eng
GR  - Aitch Fellowship/Aitch Foundation/
GR  - Dissertation completion fellowship/College of Natural Science, Michigan State 
      University/
GR  - R21CA185021/CA/NCI NIH HHS/United States
GR  - R01 MH119149/MH/NIMH NIH HHS/United States
GR  - R01CA188305/CA/NCI NIH HHS/United States
GR  - R01MH119149/NH/NIH HHS/United States
GR  - R01 CA188305/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Review
DEP - 20210509
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Protective Agents)
RN  - 9100L32L2N (Metformin)
SB  - IM
MH  - Animals
MH  - Carcinoma, Hepatocellular/etiology/metabolism/prevention & control
MH  - DNA Damage
MH  - Disease Progression
MH  - Disease Susceptibility
MH  - Hepatocytes/drug effects/metabolism
MH  - Humans
MH  - Hypoglycemic Agents/*pharmacology
MH  - Liver/*drug effects/*metabolism
MH  - Liver Neoplasms/etiology/metabolism/prevention & control
MH  - Macrophages/metabolism
MH  - Metformin/*pharmacology
MH  - Non-alcoholic Fatty Liver Disease/complications/etiology/metabolism/pathology
MH  - Oxidative Stress
MH  - Protective Agents/pharmacology
MH  - Risk Factors
PMC - PMC8126028
OTO - NOTNLM
OT  - HCC
OT  - MDSC
OT  - NAFLD
OT  - NASH
OT  - T cell
OT  - macrophage
OT  - metformin
OT  - myeloid-derived suppressor cell
OT  - type 2 diabetes mellitus
COIS- The authors declare no conflict of interest.
EDAT- 2021/06/03 06:00
MHDA- 2021/06/29 06:00
PMCR- 2021/05/09
CRDT- 2021/06/02 01:11
PHST- 2021/04/20 00:00 [received]
PHST- 2021/05/03 00:00 [revised]
PHST- 2021/05/06 00:00 [accepted]
PHST- 2021/06/02 01:11 [entrez]
PHST- 2021/06/03 06:00 [pubmed]
PHST- 2021/06/29 06:00 [medline]
PHST- 2021/05/09 00:00 [pmc-release]
AID - ijms22095016 [pii]
AID - ijms-22-05016 [pii]
AID - 10.3390/ijms22095016 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 May 9;22(9):5016. doi: 10.3390/ijms22095016.