Unraveling the Role of GABAergic-Proopiomelanocortin Neurons in the Hypothalamic Control of Energy Balance

TROTTA MILAGROS; ALSINA RAMIRO; BUMASCHNY VIVIANA

Mar del Plata

Congreso; XXX Congreso de la Sociedad Argentina de Neurociencias (SAN 2015); 2015

Obesity affects almost half a billion people worldwide. Because of the high prevalence of overweight and the severity of its comorbidities, great effort is made to unravel the neuronal circuits controlling energy balance. Hypothalamic Proopiomelanocortin (POMC) neurons are main regulators of energy balance. POMC deficient patients and mice are hyperphagic and obese. Since there are both GABAergic and glutamatergic POMC hypothalamic neurons, we speculate that both subpopulations have different connections and physiological roles. In order to characterize GABAergic-POMC neurons, we used a reversible knockout mouse model of early-onset obesity that lacks POMC expression in the hypothalamus. In this model, subsequent reactivation of POMC expression specifically in GABAergic neurons can be conditionally achieved. Before treatment at P60, hyperphagic knockout mice were ~60% heavier than their WT littermates, whereas six weeks after POMC rescue this difference dropped to ~22% and food intake completely normalized. Surprisingly, less than 20% of POMC hypothalamic neurons recovered POMC expression in these experiments, all of which are GABAergic cells. Altogether, our results suggest that the subpopulation of GABAergic POMC neurons - is probably the main regulator of food intake among POMC cells. Further experiments are undertaken to identify the target neurons of GABAergic-POMC neurons in order to elucidate the brain circuits in which they are involved.