Mini Oral ANZOS-OSSANZ-AOCO Joint Annual Scientific Meeting 2017

Phenotypic characterization of Agouti related peptide (AgRP) neurons knock out mouse for the Carnitine palmitoyl transferase 1a (CPT1a). (#195)

Mathieu Méquinion , Moyra B Lemu , Jéferson F Goularte , Alex Reichenbach , Romana Stark , Zane B Andrews

The hypothalamus is one key region of the brain in the regulation of the energy homeostatsis. Two main neuronal populations in the acruate nucleus: Agouti related peptide (AgRP) and the Pro-opimelanocortine neurons which when they are activated lead to increase or decrease the food intake, the energy expenditure, the body weight, respectively. These neurons receive various metabolic signals including nutrients and hormones. Various sensors have been proposed to regulate these functions; mounting evidence displayed a role of enzymes involved in the fatty acid metabolism in these neurons in the integration of these signals. The Cartinine Palmitoyl transferase 1a (CPT1a) is a key enzyme involved in the pool of acetyl-CoA in the mitochondria by permetting the long-chain fatty acyl-CoA to enter in the matrix and undergo the beta-oxidation. To determine the role of CPT1a in the energy metabolism we breeded AgRPCRE-IRES mice with CPT1afloxed/floxed mice to specificly deleted CPT1a in the AgRP neurons compared to the wild type (AgRPWT) mice. A complete phenotypic characterization was undertaken (body weight, food intake, body composition, plasma assays, metabolic parameters) in various metabolic conditions. Data were analyzed by Student’s t-test, two-way anova or two-way anova repetead measure.Our results displayed that AgRP CPT1a-/- mice presented no difference in the body weight and body compostion compared to the AgRPWT mice; however, in chow diet, these mice presented an higher food intake associated with a significant lower respiratory exchange ratio, and no difference for the energy expenditure or the physical activity compared to the control. In fed animals, no differences were observed in the energy metabolites and hormones ; however, in fasted condition a significant hypercorticoseronemia, hypoleptinemia and hyperinsulinemia were observed in knock out group compared to the control group. Moreover, the AgRP CPT1a-/- mice displayed an higher sensitivity to the insulin compared to the control mice.