SAN2020

Agouti-related peptide-producing neurons of the arcuate nucleus (ARC-AgRP neurons), which innervate several appetite-related brain regions, are activated in fasting states. Recently, we found that the ARC-AgRP projections to the hypothalamic paraventricular nucleus are remodeled in fasting states in a growth hormone secretagogue receptor (GHSR)-dependent manner. Here, we tested if the fasting-induced activation of ARC-AgRP neurons promotes morphological remodeling of other hypothalamic (lateral hypothalamic area, LHA) and extra-hypothalamic (paraventricular thalamus, PVT, and central amygdala, CeA) ARC-AgRP projections and its dependence on GHSR. We performed fluorescent immunostaining against AgRP in brains of ad libitum fed or fasted mice with pharmacological or genetic blockage of the GHSR signaling and estimated the density and strength of ARC-AgRP fibers. We found that: 1) the density and strength of ARC-AgRP fibers increase in the LHA of fasted mice, whereas no differences were detected in the PVT and CeA. 2) Fasting-induced increase of the marker of neuronal activation c-Fos in the LHA was abrogated in ARC-ablated mice. 3) Fasting-induced remodeling of ARC-AgRP→LHA projections was not affected in mice with pharmacological or genetic blockage of GHSR signaling. This evidence shows that the remodeling of the ARC-AgRP fibers in fasting state occurs in a brain region-dependent manner and that the GHSR activity does not regulate this phenomenon in the LHA.