Identification of a subpopulation of proopiomelanocortin neurons with a major role in energy balance

ALSINA, RAMIRO; TROTTA, MILAGROS; BUMASCHNY, VIVIANA FLORENCIA

Mar del Plata, Buenos Aires, Argentina

Congreso; XXX II Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; 2017

Sociedad Argentina de Investigación en Neurociencia (SAN)

The hypothalamus is a main regulator of energy balance and glucose homeostasis. In particular, proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus sense the energy status of the organism by the integration of peripheral signals. In turn, POMC neurons coordinate energy balance by decreasing food intake and promoting energy expenditure, and facilitate glucose utilization. Some studies demonstrated the existence of two subpopulations of POMC neurons expressing GABA or glutamate. Considering the opposite responses elicited by these neurotransmitters, we hypothesize that both subpopulations have different physiological roles. In order to prove this hypothesis, we first characterized GABAergic-POMC neurons by using obese mice bearing a reversible mutation that prevents arcuate POMC expression. Interestingly, specific Pomc re-expression only in GABAergic neurons, significantly decreased body weight and completely restored food intake and metabolic efficiency. Surprisingly, these improvements were achieved by rescuing only 25% of total arcuate POMC neurons. Finally, immunohistochemical analysis showed that GABAergic-POMC neurons preferentially project to the dorsolateral hypothalamus (DMH), a nucleus that induces food intake by releasing NPY. Altogether, these results suggest that GABAergic Pomc neurons participate in an arcuate-DMH circuit with a major role in the regulation of energy balance and glucose metabolism.