IFIBIO HOUSSAY 25014
INSTITUTO DE FISIOLOGIA Y BIOFISICA BERNARDO HOUSSAY
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Hypothalamic proopiomelanocortin expression restricted to GABAergic neurons prevents overfeeding and Neuropeptide Y overexpression
Autor/es:
TROTTA, MILAGROS; FERRÁN, JOSÉ LUIS; TROTTA, MILAGROS; FERRÁN, JOSÉ LUIS; ALSINA, RAMIRO; BUMASCHNY, VIVIANA FLORENCIA; ALSINA, RAMIRO; BUMASCHNY, VIVIANA FLORENCIA; BELLO, ESTEFANÍA PILAR; RUBINSTEIN, MARCELO; BELLO, ESTEFANÍA PILAR; RUBINSTEIN, MARCELO
Lugar:
On line
Reunión:
Congreso; XXXV Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias; 2020
Institución organizadora:
Sociedad Argentina de Investigación en Neurociencias (SAN)
Resumen:
The arcuate nucleus of the hypothalamus is a key regulator of energy homeostasis where different neuronal populations integrate peripheral signals of energy status, and project to the hypothalamus and other brain areas. In particular, arcuate proopiomelanocortin (POMC) neurons inhibit food intake and promote energy expenditure. POMC neurons co-secrete either glutamate (7%) or GABA (40%). Considering the antagonic responses these neurotransmitters elicit, we hypothesize that both subpopulations have different physiological roles. In order to elucidate the role of GABAergic POMC neurons, we intercrossed hyperphagic and obese mice bearing a reversible mutation that prevents arcuate POMC expression, with another line expressing a GABA-specific Cre driver. We found that Pomc rescue restricted to GABAergic neurons leads to food intake and metabolic efficiency normalization. Surprisingly, these physiological improvements were achieved with the recovery of Pomc expression in only 25% of total hypothalamic POMC neurons. Immunohistochemical analysis showed that GABAergic POMC neurons preferentially project to the dorsomedial hypothalamus (DMH), a nucleus that induces food intake by releasing NPY. Interestingly, we found NPY expression in the DMH of POMC deficient but not of WT mice. Finally, NPY expression is highly reduced after POMC recovery. Altogether, these results show that GABAergic POMC neurons have a major role in the regulation of energy balance, probably by regulating NPY expression in the DMH.
