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Hypothalamic proopiomelanocortin expression restricted to GABAergic neurons prevents overfeeding and Neuropeptide Y overexpression

Milagros Trotta

  • Ciudad Autónoma de Buenos Aires,
  • Argentina
  • Milagros Trotta ¹
  • , Estefania Pilar Bello ¹
  • , Ramiro Alsina ¹
  • , José Luis Ferrán ⁴
  • , Marcelo Rubinstein ³
  • , Viviana Florencia Bumaschny ¹𝄒²
  • 1 Grupo de Neurociencias de Sistemas, Instituto de Fisiología y Biofísica "Bernardo Houssay" (IFIBIO, UBA-CONICET)
  • 2 Departamento de Fisiología, Facultad de Medicina, Universidad de Buenos Aires.
  • 3 Instituto de Investigaciones en Ingeniería Genética y Biología Molecular “Dr. Héctor N. Torres”. INGEBI (CONICET)
  • 4 Departamento de Anatomía Humana y Psicobiología, Facultad de Medicina, Universidad de Murcia, España

The arcuate nucleus is a key regulator of energy homeostasis in which different neuronal populations integrate peripheral signals of energy status. In particular, arcuate proopiomelanocortin (POMC) neurons inhibit food intake and promote energy expenditure. Due to the existence of different subpopulations of POMC neurons secreting antagonistic neurotransmitters such as glutamate or GABA, it is proposed that Arc-POMC neurons could have different physiological roles and targets. In the present study, we aimed to elucidate the contribution of the subpopulation of Arc-POMC GABAergic neurons in the control of energy balance by expressing Pomc exclusively in GABAergic-POMC neurons. We found that Pomc rescue restricted to GABAergic neurons leads to food intake normalization and body weight enhancement. 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. In addition, we found that DMH-NPY expression is negatively correlated with Pomc expression in GABAergic-POMC neurons, suggesting that food intake may be regulated by an Arc-GABAergic-POMC→ DMH-NPY pathway.