In the acruate nucleus of the hypothalamus, a key region in the energy homeostasis regulation, the Agouti related peptide (AgRP) neurons were largely described to be involved in this function. These neurons receive various metabolic signals including nutrients and hormones. Growing evidence displayed a role of the fatty acid metabolism in these neurons in their integration. The Carnitine Palmitoyl Transferase1a is a key enzyme involved in the pool of acetyl-CoA in the mitochondria by permitting the long-chain fatty acyl-CoA to enter into the matrix and undergo the beta-oxidation. Previous works have shown that this enzyme is involved in the food intake and glucose homeostasis.
To determine the role of CPT1a in the energy homeostasis, we breeded AgRPCRE-IRES mice with CPT1afloxed/floxed mice to specifically 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). Data were analyzed by Student’s t-test, two-way anova or two-way anova repetead measure.
Although the AgRP CPT1a-/- mice presented sligh higher food intake no difference in the body weight and body composition were observed compared to the AgRPWT mice. In parallel, in fed and fasted conditions no difference was observed for the energy metabolism and plasmatic parameters. However, the AgRP CPT1a-/- mice presented a higher plasma insulin secretion induce by the glucose. The next step will be to focus on the hypothalamic impact of the knockout as well as the AgRP neurons sensitivity to the insulin.