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PGC-1β Induces Susceptibility To Acetaminophen-Driven Acute Liver Failure.
- Source :
-
Scientific reports [Sci Rep] 2019 Nov 14; Vol. 9 (1), pp. 16821. Date of Electronic Publication: 2019 Nov 14. - Publication Year :
- 2019
-
Abstract
- Acetaminophen (APAP) is a worldwide commonly used painkiller drug. However, high doses of APAP can lead to acute hepatic failure and, in some cases, death. Previous studies indicated that different factors, including life-style and metabolic diseases, could predispose to the risk of APAP-induced liver failure. However, the molecular process that could favor APAP hepatotoxicity remains understood. Here, we reported that a short-term high fat-enriched diet worsens APAP-induced liver damage, by promoting liver accumulation of lipids that induces the activation of peroxisome proliferator-activated receptor gamma coactivator 1-beta (PGC-1β). Therefore, we challenged mice with hepatic-specific PGC-1β overexpression on a chow diet with a subtoxic dose of APAP and we found that PGC-1β overexpression renders the liver more sensitive to APAP damage, mainly due to intense oxidative stress, finally ending up with liver necrosis and mice death. Overall, our results indicated that during high fat feeding, PGC-1β adversely influences the ability of the liver to overcome APAP toxicity by orchestrating different metabolic pathways that finally lead to fatal outcome.
- Subjects :
- Animals
Disease Models, Animal
Liver metabolism
Liver Failure, Acute chemically induced
Liver Failure, Acute genetics
Male
Mice
Mice, Inbred C57BL
Oxidative Stress
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha metabolism
Acetaminophen adverse effects
Diet, High-Fat adverse effects
Liver Failure, Acute metabolism
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 9
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 31727907
- Full Text :
- https://doi.org/10.1038/s41598-019-53015-6