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 [Lipids]

Chronic high-fat diet (HFD) 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 pathway and PPARα 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 HFD or obesity induced metabolic diseases by improving mitochondrial lipid and ROS metabolism.

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