An analogue of the Prolactin Releasing Peptide reduces obesity and promotes adult neurogenesis

Abstract

Hypothalamic Adult Neurogenesis (hAN) has been implicated in regulating energy homeostasis. Adult-generated neurons and adult Neural Stem Cells (aNSCs) in the hypothalamus control food intake and body weight. Conversely, diet-induced obesity (DIO) by high fat diets (HFD) exerts adverse influence on hAN. However, the effects of anti-obesity compounds on hAN are not known. To address this, we administered a lipidized analogue of an anti-obesity neuropeptide, Prolactin Releasing Peptide (PrRP), so-called LiPR, to mice. In the HFD context, LiPR rescued the survival of adult-born hypothalamic neurons and increased the number of aNSCs by reducing their activation. LiPR also rescued the reduction of immature hippocampal neurons and modulated calcium dynamics in iPSC-derived human neurons. In addition, some of these neurogenic effects were exerted by another anti-obesity compound, Liraglutide. These results show for the first time that anti-obesity neuropeptides influence adult neurogenesis and suggest that the neurogenic process can serve as a target of anti-obesity pharmacotherapy.

Anorexigenic neuropeptides as anti-obesity and neuroprotective agents

“…Moreover, palm 11 -PrRP31 increased synaptic plasticity [ 54 , 190 ], neurogenesis manifested as an increase in doublecortin-positive cells in the hippocampal DG [ 54 ], and decreased apoptosis in the hippocampus [ 190 ]. Recently, a beneficial effect on adult neurogenesis, which was impaired in DIO mice, was described [ 192 ]. The possible implication of PrRP and GPR10 for proper brain function was stressed by the recent finding that decreased GPR10 receptor levels were observed in patients with AD [ 193 ].…”