Neuroendocrinology and Neuroimmunology
Author: Franco Barrile Barrile | email: francobarrile@gmail.com
Franco Barrile 1°, Daniela Cassano 2°, Guadalupe García Romero 1°, Mario Perelló 1°
1° CONICET
2° Agencia (MINCyT)
Ghrelin is a stomach-derived hormone that promotes a variety of functions and acts via the growth hormone secretagogue receptor (GHSR). GHSR is highly expressed in the brain including the arcuate nucleus (ARC) and the lateral hypothalamic area (LHA), both regions involved in energy balance, feeding and reward-related behaviors, among others. Within the LHA, the orexin (LHAorexin) neurons have been suggested to be key mediators of ghrelins actions. Here we wanted to gain insights into the role of the LHAorexin neurons and its connections to the ARC nucleus mediating the orexigenic effects of ghrelin. First, we tested the effect of ghrelin administration into the LHA of male mice and found that it increases food intake and cFos induction in the LHAorexin neurons and in the ARC nucleus. Using ARC-ablated mice, we found that ARC is necessary to increase food intake after intra-LHA ghrelin administration. Also, we found that the injection of an orexin 1 receptor antagonist (SB) blocked the increase in food intake induced by intra-LHA ghrelin administration. In terms of the neuronal populations involved in these changes, we showed that intra-LHA ghrelin administration increases cFos induction in ARCNPY neurons and that such effect is abrogated by SB treatment. Strikingly, LHAorexin neurons did not express GHSR. Our results indicate that ghrelin action in the LHA indirectly activate orexin neurons, which in turn induced the activation of the ARCNPY and increased food intake.