PMID- 35052597
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220128
IS  - 2076-3921 (Print)
IS  - 2076-3921 (Electronic)
IS  - 2076-3921 (Linking)
VI  - 11
IP  - 1
DP  - 2021 Dec 30
TI  - Gallic Acid Improves Diabetic Steatosis by Downregulating MicroRNA-34a-5p through 
      Targeting NFE2L2 Expression in High-Fat Diet-Fed db/db Mice.
LID - 10.3390/antiox11010092 [doi]
LID - 92
AB  - Type 2 diabetes mellitus (T2DM) has become epidemic worldwide and is strongly 
      associated with nonalcoholic fatty liver disease (NAFLD). The molecular 
      mechanisms of microRNAs in NAFLD and T2DM development and the corresponding 
      therapies remain unclear. We performed microRNA microarray validation to 
      determine whether hepatic miR-34a-5p was significantly upregulated in db/db mice 
      fed with a high-fat diet (HFD), a mouse model of T2DM with steatohepatitis. The 
      potential role of miR-34a-5p and gallic acid (GA) in regulating hepatic lipid 
      metabolism and diabetic steatosis was explored. GA improved the activities of 
      antioxidant enzymes and suppressed lipid accumulation in the HFD-induced 
      steatotic liver of db/db mice. In vitro, the silencing of miR-34a-5p in 
      hepatocyte HepG2 cells ameliorated high glucose + oleic acid/palmitic acid 
      mixture-induced accumulation of cellular triglycerides. We identified nuclear 
      factor erythroid-derived 2-like 2 (NFE2L2) as a direct target of miR-34a-5p. 
      Reduction in intracellular triglyceride and the expression levels of sterol 
      regulatory element-binding protein 1 and fatty acid synthase by GA were mediated 
      by the inhibition of miR-34a-5p expression in HepG2 cells. The findings suggest 
      that GA improves hepatic lipogenesis by downregulating miR-34a-5p by suppressing 
      NFE2L2 expression, indicating the potential therapeutic role of GA or an 
      NFE2L2-activating agent in diabetic fatty liver disease.
FAU - Lee, Ang-Tse
AU  - Lee AT
AUID- ORCID: 0000-0002-5587-9409
AD  - Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.
AD  - Wang Chin-Yao Clinic, Taichung 408, Taiwan.
FAU - Yang, Mon-Yuan
AU  - Yang MY
AD  - Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.
FAU - Lee, Yi-Ju
AU  - Lee YJ
AD  - Department of Pathology, Chung Shan Medical University Hospital, Taichung 402, 
      Taiwan.
AD  - Department of Pathology, Chung Shan Medical University, Taichung 402, Taiwan.
FAU - Yang, Tzu-Wei
AU  - Yang TW
AD  - Division of Gastroenterology and Hepatology, Department of Internal Medicine, 
      Chung Shan Medical University Hospital, Taichung 402, Taiwan.
AD  - School of Medical, Chung Shan Medical University, Taichung 402, Taiwan.
FAU - Wang, Chi-Chih
AU  - Wang CC
AD  - Division of Gastroenterology and Hepatology, Department of Internal Medicine, 
      Chung Shan Medical University Hospital, Taichung 402, Taiwan.
AD  - School of Medical, Chung Shan Medical University, Taichung 402, Taiwan.
FAU - Wang, Chau-Jong
AU  - Wang CJ
AD  - Department of Health Industry Technology Management, Chung Shan Medical 
      University, Taichung 402, Taiwan.
AD  - Department of Medical Research, Chung Shan Medical University Hospital, Taichung 
      402, Taiwan.
LA  - eng
GR  - MOST 109-2320-B-040 -024-/Ministry of Science and Technology Grant, Taiwan/
PT  - Journal Article
DEP - 20211230
PL  - Switzerland
TA  - Antioxidants (Basel)
JT  - Antioxidants (Basel, Switzerland)
JID - 101668981
PMC - PMC8773012
OTO - NOTNLM
OT  - NFE2L2
OT  - diabetic steatosis
OT  - gallic acid
OT  - lipogenesis
OT  - microRNA
COIS- The authors declare no conflict of interest.
EDAT- 2022/01/22 06:00
MHDA- 2022/01/22 06:01
PMCR- 2021/12/30
CRDT- 2022/01/21 01:03
PHST- 2021/11/30 00:00 [received]
PHST- 2021/12/24 00:00 [revised]
PHST- 2021/12/28 00:00 [accepted]
PHST- 2022/01/21 01:03 [entrez]
PHST- 2022/01/22 06:00 [pubmed]
PHST- 2022/01/22 06:01 [medline]
PHST- 2021/12/30 00:00 [pmc-release]
AID - antiox11010092 [pii]
AID - antioxidants-11-00092 [pii]
AID - 10.3390/antiox11010092 [doi]
PST - epublish
SO  - Antioxidants (Basel). 2021 Dec 30;11(1):92. doi: 10.3390/antiox11010092.