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Metformin Alleviates Hepatic Steatosis and Insulin Resistance in a Mouse Model of High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease by Promoting Transcription Factor EB-Dependent Autophagy
- Source :
- Frontiers in Pharmacology, Vol 12 (2021), Frontiers in Pharmacology
- Publication Year :
- 2021
- Publisher :
- Frontiers Media S.A., 2021.
-
Abstract
- Nonalcoholic fatty liver disease (NAFLD) results from an abnormal accumulation of lipids within hepatocytes, and is commonly associated with obesity, insulin resistance, and hyperlipidemia. Metformin is commonly used to treat type 2 diabetes mellitus and, in recent years, it was found to play a potential role in the amelioration of NAFLD. However, the mechanisms underlying the protective effect of metformin against NAFLD remain largely unknown. Transcription factor EB (TFEB) is a master transcriptional regulator of lysosomal biogenesis and autophagy and, when activated, is effective against disorders of lipid metabolism. However, the role of TFEB in hepatic steatosis is not well understood. In this report, we demonstrate that the activity of TFEB is reduced in the liver of mice fed a high-fat diet. Metformin treatment significantly reverses the activity of TFEB, and the protective effect of metformin against hepatic steatosis and insulin resistance is dependent on TFEB. We show that metformin-induced autophagy is regulated by TFEB, and our findings reveal that TFEB acts as a mediator, linking metformin with autophagy to reverse NAFLD, and highlight that TFEB may be a promising molecular target for the treatment of NAFLD.
- Subjects :
- 0301 basic medicine
nonalcoholic fatty liver disease
medicine.medical_specialty
autophagy
endocrine system diseases
RM1-950
03 medical and health sciences
0302 clinical medicine
Insulin resistance
Internal medicine
insulin resistance
Nonalcoholic fatty liver disease
medicine
Pharmacology (medical)
Original Research
Pharmacology
TFEB
business.industry
hepatic steatosis
Autophagy
Type 2 Diabetes Mellitus
nutritional and metabolic diseases
Lipid metabolism
medicine.disease
Metformin
030104 developmental biology
Endocrinology
030220 oncology & carcinogenesis
Therapeutics. Pharmacology
Steatosis
business
metformin
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 16639812
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Frontiers in Pharmacology
- Accession number :
- edsair.doi.dedup.....b3a9ed740c5a53e929d96008bf3ec4dd
- Full Text :
- https://doi.org/10.3389/fphar.2021.689111/full