Peroxisomes as mediators of the metabolic effects of fish oil in obesity and associated metabolic diseases

Abstract

We propose herein to investigate the role of peroxisomes as mediators of the beneficial and protective effects of n-3 long chain polyunsaturated fatty acids (omega 3 FA) against obesity and associated metabolic diseases. More specifically, we will investigate whether hepatocyte and adipocyte peroxisome deficiency (Pex5 deletion) affects the pro-energy expenditure, insulin sensitizing and anti-inflammatory actions of n-3 fatty acids. For this, mice bearing or not deletion of Pex5 in hepatocytes or adipocytes, will be fed high-fat diets produced using as fat source either lard or fish oil enriched with the n-3 fatty acids eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA) for 8-12 weeks and evaluated for body weight, food intake, energy expenditure, body temperature, adiposity, glucose homeostasis (GTT, ITT and PTT), mitochondrial fatty acid oxidation, respiration and uncoupling, peroxisomal fatty acid oxidation and hydrogen peroxide production, metabolic (futile) cycling, liver and adipose tissue oxidative stress, inflammation, insulin signaling and lipidome and metabolic genes/proteins. In addition, murine hepatocytes and adipocytes bearing or not peroxisome deficiency (Pex5 deletion) will be evaluated for oxygen consumption, fatty acid oxidation, glucose metabolism and oxidative stress after treatment with EPA and/or DHA. This proposal was cooperatively developed by USP and TTU teams and represents the continuation of a successful collaboration between Dr Moustaid-Moussa and Dr Festuccia laboratories over the last 4 years. (AU)