title: 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.
abstract: 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.
authors.affiliation: From the School of Life Science, Hunan University of Science and Technology, Xiangtan, Hunan 411201, China zengj@hnu.edu.cn.
authors.forename: Jia
authors.initials: J
authors.lastname: Zeng
authors.affiliation: From the School of Life Science, Hunan University of Science and Technology, Xiangtan, Hunan 411201, China.
authors.forename: Senwen
authors.initials: S
authors.lastname: Deng
authors.affiliation: From the School of Life Science, Hunan University of Science and Technology, Xiangtan, Hunan 411201, China.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Wang
authors.affiliation: From the School of Life Science, Hunan University of Science and Technology, Xiangtan, Hunan 411201, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: From the School of Life Science, Hunan University of Science and Technology, Xiangtan, Hunan 411201, China.
authors.forename: Lian
authors.initials: L
authors.lastname: Tang
authors.affiliation: From the School of Life Science, Hunan University of Science and Technology, Xiangtan, Hunan 411201, China.
authors.forename: Yefeng
authors.initials: Y
authors.lastname: Pang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D042962:Acyl-CoA Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001835:Body Weight; D059305:Diet, High-Fat; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D008055:Lipids / Q000737:chemistry*; D008099:Liver / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D010100:Oxygen / Q000737:chemistry; D020675:Peroxisomes / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D056564:Sirtuin 1 / Q000378:metabolism
chemical_list: C434762:10,12-tricosadiynoic acid; D005231:Fatty Acids, Unsaturated; D007328:Insulin; D008055:Lipids; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D042962:Acyl-CoA Oxidase; D055372:AMP-Activated Protein Kinases; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D010100:Oxygen
keywords: acetyl coenzyme A (acetyl-CoA); fatty acid; fatty acid metabolism; fatty acid oxidation; inhibitor; metabolism