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PTUPB ameliorates high-fat diet-induced non-alcoholic fatty liver disease via inhibiting NLRP3 inflammasome activation in mice.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2020 Mar 19; Vol. 523 (4), pp. 1020-1026. Date of Electronic Publication: 2020 Jan 20. - Publication Year :
- 2020
-
Abstract
- Non-alcoholic fatty liver disease (NAFLD) affects 25% of the global adult population, and no effective pharmacological treatment has been found. Products of arachidonic acid metabolism have been developed into a novel therapy for metabolic syndrome and diabetes. It has been demonstrated that protective actions of a novel dual cyclooxygenase-2 (COX-2) and soluble epoxide hydrolase (sEH) inhibitor, PTUPB, on the metabolic abnormalities. Here, we investigated the effects of PTUPB on hepatic steatosis in high-fat diet (HFD)-induced obese mice, as well as in hepatocytes in vitro. We found that PTUPB treatment reduced body weight, liver weight, liver triglyceride and cholesterol content, and the expression of lipolytic/lipogenic and lipid uptake related genes (Acc, Cd36, and Cidec) in HFD mice. In addition, PTUPB treatment arrested fibrotic progression with a decrease of collagen deposition and expression of Col1a1, Col1a3, and α-SMA. In vitro, PTUPB decreased palmitic acid-induced lipid deposition and downregulation of lipolytic/lipogenic genes (Acc and Cd36) in hepatocytes. Additionally, we found that PTUPB reduced the production of pro-inflammatory cytokines and suppressed the NLRP3 inflammasome activation in HFD mice and hepatocytes. In conclusion, dual inhibition of COX-2/sEH attenuates hepatic steatosis by inhibiting the NLRP3 inflammasome activation. PTUPB might be a promising potential therapy for liver steatosis associated with obesity.<br />Competing Interests: Declaration of competing interest The authors declare no competing financial interests.<br /> (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Cell Line
Cyclooxygenase 2 metabolism
Epoxide Hydrolases metabolism
Inflammation pathology
Liver enzymology
Liver pathology
Liver Cirrhosis enzymology
Liver Cirrhosis pathology
Male
Mice, Inbred C57BL
Non-alcoholic Fatty Liver Disease enzymology
Non-alcoholic Fatty Liver Disease pathology
Diet, High-Fat adverse effects
Inflammasomes metabolism
NLR Family, Pyrin Domain-Containing 3 Protein metabolism
Non-alcoholic Fatty Liver Disease drug therapy
Non-alcoholic Fatty Liver Disease metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 523
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 31973813
- Full Text :
- https://doi.org/10.1016/j.bbrc.2019.12.131