PMID- 36238196
OWN - NLM
STAT- MEDLINE
DCOM- 20221017
LR  - 20221101
IS  - 1177-8881 (Electronic)
IS  - 1177-8881 (Linking)
VI  - 16
DP  - 2022
TI  - Semaglutide May Alleviate Hepatic Steatosis in T2DM Combined with NFALD Mice via 
      miR-5120/ABHD6.
PG  - 3557-3572
LID - 10.2147/DDDT.S384884 [doi]
AB  - OBJECTIVE: Although the pathogenesis of non-alcoholic fatty liver disease (NAFLD) 
      has been extensively studied, the role of its underlying pathogenesis remains 
      unclear, and there is currently no approved therapeutic strategy for NAFLD. The 
      purpose of this study was to observe the beneficial effects of Semaglutide on 
      NAFLD in vivo and in vitro, as well as its potential molecular mechanisms. 
      METHODS: Semaglutide was used to treat type 2 diabetes mellitus (T2DM) combined 
      with NAFLD mice for 12 weeks. Hepatic function and structure were evaluated by 
      liver function, blood lipids, liver lipids, H&E staining, oil red staining and 
      Sirius staining. The expression of alpha/beta hydrolase domain-6 (ABHD6) was measured by 
      qPCR and Western blotting in vivo and in vitro. Then, dual-luciferase reporter 
      assay was performed to verify the regulation of the upstream miR-5120 on ABHD6. 
      RESULTS: Our data revealed that Semaglutide administration significantly improved 
      liver function and hepatic steatosis in T2DM combined with NAFLD mice. 
      Furthermore, compared with controls, up-regulation of ABHD6 and down-regulation 
      of miR-5120 were found in the liver of T2DM+NAFLD mice and HG+FFA-stimulated Hepa 
      1-6 hepatocytes. Interestingly, after Semaglutide intervention, ABHD6 expression 
      was significantly decreased in the liver of T2DM+NAFLD mice and in 
      HG+FFA-stimulated Hepa 1-6 hepatocytes, while miR-5120 expression was increased. 
      We also found that miR-5120 could regulate the expression of ABHD6 in 
      hepatocytes, while Semaglutide could modulate the expression of ABHD6 through 
      miR-5120. In addition, GLP-1R was widely expressed in mouse liver tissues and 
      Hepa 1-6 cells. Semaglutide could regulate miR-5120/ABHD6 expression through 
      GLP-1R. CONCLUSION: Our data revealed the underlying mechanism by which 
      Semaglutide improves hepatic steatosis in T2DM+NAFLD, and might shed new light on 
      the pathological role of miR-5120/ABHD6 in the pathogenesis of T2DM+NAFLD.
CI  - (c) 2022 Li et al.
FAU - Li, Ran
AU  - Li R
AUID- ORCID: 0000-0003-2304-6282
AD  - Department of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, 
      Tongji University, Shanghai, People's Republic of China.
FAU - Ye, Zhengqin
AU  - Ye Z
AD  - Department of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, 
      Tongji University, Shanghai, People's Republic of China.
FAU - She, Dunmin
AU  - She D
AD  - Clinical Medical College, Yangzhou University, Yangzhou, People's Republic of 
      China.
AD  - Department of Endocrinology, Northern Jiangsu People's Hospital Affiliated to 
      Yangzhou University, Yangzhou, People's Republic of China.
FAU - Fang, Ping
AU  - Fang P
AD  - Department of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, 
      Tongji University, Shanghai, People's Republic of China.
FAU - Zong, Guannan
AU  - Zong G
AD  - Department of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, 
      Tongji University, Shanghai, People's Republic of China.
FAU - Hu, Kerong
AU  - Hu K
AD  - Department of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, 
      Tongji University, Shanghai, People's Republic of China.
FAU - Kong, Dehong
AU  - Kong D
AD  - Department of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, 
      Tongji University, Shanghai, People's Republic of China.
FAU - Xu, Wei
AU  - Xu W
AD  - Department of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, 
      Tongji University, Shanghai, People's Republic of China.
FAU - Li, Ling
AU  - Li L
AD  - Department of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, 
      Tongji University, Shanghai, People's Republic of China.
FAU - Zhou, Yun
AU  - Zhou Y
AD  - Department of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, 
      Tongji University, Shanghai, People's Republic of China.
FAU - Zhang, Keqin
AU  - Zhang K
AD  - Department of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, 
      Tongji University, Shanghai, People's Republic of China.
FAU - Xue, Ying
AU  - Xue Y
AUID- ORCID: 0000-0002-6812-5665
AD  - Department of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, 
      Tongji University, Shanghai, People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20221012
PL  - New Zealand
TA  - Drug Des Devel Ther
JT  - Drug design, development and therapy
JID - 101475745
RN  - 0 (MicroRNAs)
RN  - 53AXN4NNHX (semaglutide)
RN  - 62340-29-8 (Glucagon-Like Peptides)
RN  - EC 3.1.1.23 (ABHD6 protein, mouse)
RN  - EC 3.1.1.23 (Monoacylglycerol Lipases)
SB  - IM
MH  - Animals
MH  - *Diabetes Mellitus, Type 2/metabolism
MH  - Glucagon-Like Peptides
MH  - Liver/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - *MicroRNAs/genetics/metabolism
MH  - Monoacylglycerol Lipases/metabolism
MH  - *Non-alcoholic Fatty Liver Disease/metabolism
PMC - PMC9553160
OTO - NOTNLM
OT  - Semaglutide
OT  - microRNA-5120
OT  - non-alcoholic fatty liver disease
OT  - type 2 diabetes mellitus
OT  - alpha/beta hydrolase domain-6
COIS- The authors declare that they have no conflict of interest.
EDAT- 2022/10/15 06:00
MHDA- 2022/10/18 06:00
PMCR- 2022/10/12
CRDT- 2022/10/14 03:01
PHST- 2022/08/03 00:00 [received]
PHST- 2022/10/06 00:00 [accepted]
PHST- 2022/10/14 03:01 [entrez]
PHST- 2022/10/15 06:00 [pubmed]
PHST- 2022/10/18 06:00 [medline]
PHST- 2022/10/12 00:00 [pmc-release]
AID - 384884 [pii]
AID - 10.2147/DDDT.S384884 [doi]
PST - epublish
SO  - Drug Des Devel Ther. 2022 Oct 12;16:3557-3572. doi: 10.2147/DDDT.S384884. 
      eCollection 2022.