UCP1-independent mechanisms involved in the increased energy expenditure and protection against Obesity induced by fish oil in mice

Abstract

Intake of a high fat diet rich in fish oil and omega 3 fatty acids (n-3 fatty acids) protects mice from body weight gain and Obesity by increasing energy expenditure in an UCP1-independent manner. We will investigate herein the involvement skeletal muscle, heart and liver peroxisomal and mitochondrial oxidative metabolism, as well as SERCA-mediated calcium cycling as mediators of the increased in energy expenditure induced by intake of a high fat diet rich in fish oil. For this, wild type and UCP1 KO mice will be fed for 8 weeks with high fat diet produced using either lard (HFD) or fish oil (HFN3) as fat source and evaluated for body weight, adiposity, indirect calorimetry, body temperature, mitochondrial function, expression and content of enzymes involved in peroxisomal and mitochondrial beta-oxidation and biogenesis. In a second protocol, these parameters will be evaluated in wild type and UCP1 KO mice fed during 4 weeks with either HFD or HFN3 and treated with the pharmacological inhibitor of acyl-CoA oxidase (ACOX-1) 10,12-tricosadiynoic acid (100 mg/kg, gavagem). In a third protocol, these parameters will be evaluated in controls and in mice with PEX-5 deficiency exclusively in hepatocytes. (AU)