Specific Inhibition of Acyl-CoA Oxidase-1 by an Acetylenic Acid Improves Hepatic Lipid and Reactive Oxygen Species (ROS) Metabolism in Rats Fed a High Fat Diet

Specific Inhibition of Acyl-CoA Oxidase-1 by an Acetylenic Acid Improves Hepatic Lipid and Reactive Oxygen Species (ROS) Metabolism in Rats Fed a High Fat Diet

A chronic high fat diet results in hepatic mitochondrial dysfunction and induction of peroxisomal fatty acid oxidation (FAO); whether specific inhibition of peroxisomal FAO benefits mitochondrial FAO and reactive oxygen species (ROS) metabolism remains unclear. In this study a specific inhibitor for...

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Published in:The Journal of biological chemistry Vol. 292; no. 9; pp. 3800 - 3809
Main Authors: Zeng, Jia, Deng, Senwen, Wang, Yiping, Li, Ping, Tang, Lian, Pang, Yefeng
Format: Journal Article
Language:English
Published: United States Elsevier Inc 03-03-2017
American Society for Biochemistry and Molecular Biology
Subjects:
acetyl coenzyme A (acetyl-CoA)
Acyl-CoA Oxidase - antagonists & inhibitors
Acyl-CoA Oxidase - metabolism
AMP-Activated Protein Kinases - metabolism
Animals
Body Weight
Diet, High-Fat
fatty acid
fatty acid metabolism
fatty acid oxidation
Fatty Acids, Unsaturated - pharmacology
inhibitor
Insulin - metabolism
Lipids - chemistry
Liver - metabolism
Male
Metabolism
Mitochondria - metabolism
Oxygen - chemistry
Peroxisomes - metabolism
Rats
Rats, Wistar
Reactive Oxygen Species - metabolism
Recombinant Proteins - metabolism
Sirtuin 1 - metabolism
fatty acid
metabolism
fatty acid oxidation
inhibitor
fatty acid metabolism
acetyl coenzyme A (acetyl-CoA)
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Summary:A chronic high fat diet results in hepatic mitochondrial dysfunction and induction of peroxisomal fatty acid oxidation (FAO); whether specific inhibition of peroxisomal FAO benefits mitochondrial FAO and reactive oxygen species (ROS) metabolism remains unclear. In this study a specific inhibitor for the rate-limiting enzyme involved in peroxisomal FAO, acyl-CoA oxidase-1 (ACOX1) was developed and used for the investigation of peroxisomal FAO inhibition upon mitochondrial FAO and ROS metabolism. Specific inhibition of ACOX1 by 10,12-tricosadiynoic acid increased hepatic mitochondrial FAO via activation of the SIRT1-AMPK (adenosine 5′-monophosphate-activated protein kinase) pathway and proliferator activator receptor α and reduced hydrogen peroxide accumulation in high fat diet-fed rats, which significantly decreased hepatic lipid and ROS contents, reduced body weight gain, and decreased serum triglyceride and insulin levels. Inhibition of ACOX1 is a novel and effective approach for the treatment of high fat diet- or obesity-induced metabolic diseases by improving mitochondrial lipid and ROS metabolism.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
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Edited by Dennis R. Voelker
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M116.763532