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Hepatocytic Activating Transcription Factor 3 Protects Against Steatohepatitis via Hepatocyte Nuclear Factor 4α
- Source :
- Diabetes
- Publication Year :
- 2021
- Publisher :
- American Diabetes Association, 2021.
-
Abstract
- Activating transcription factor 3 (ATF3) has been shown to play an important role in HDL metabolism; yet, the role of hepatocytic ATF3 in the development of steatohepatitis remains elusive. Here we show that adenoassociated virus-mediated overexpression of human ATF3 in hepatocytes prevents diet-induced steatohepatitis in C57BL/6 mice and reverses steatohepatitis in db/db mice. Conversely, global or hepatocyte-specific loss of ATF3 aggravates diet-induced steatohepatitis. Mechanistically, hepatocytic ATF3 induces hepatic lipolysis and fatty acid oxidation and inhibits inflammation and apoptosis. We further show that hepatocyte nuclear factor 4α (HNF4α) is required for ATF3 to improve steatohepatitis. Thus, the current study indicates that ATF3 protects against steatohepatitis through, at least in part, hepatic HNF4α. Targeting hepatic ATF3 may be useful for treatment of steatohepatitis.
- Subjects :
- Kupffer Cells
Endocrinology, Diabetes and Metabolism
Activating transcription factor
Inflammation
Mice
Mice, Inbred NOD
Non-alcoholic Fatty Liver Disease
Hepatic Stellate Cells
Internal Medicine
medicine
Animals
Humans
Lipolysis
RNA, Messenger
Beta oxidation
Mice, Knockout
ATF3
Activating Transcription Factor 3
Chemistry
medicine.disease
Mice, Inbred C57BL
MicroRNAs
Hepatocyte nuclear factors
Metabolism
Gene Expression Regulation
Hepatocyte Nuclear Factor 4
Diet, Western
Apoptosis
Hepatocytes
Cancer research
medicine.symptom
Steatohepatitis
Subjects
Details
- ISSN :
- 00121797
- Volume :
- 70
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi.dedup.....1780b03efe272ff85a80080b8d54341b