Abstract
AbstractHypothalamic 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. In the HFD context, LiPR rescued survival of adult-born hypothalamic neurons and increased the number of aNSCs by reducing their activation. In addition, LiPR rescued reduction of immature hippocampal neurons and modulated calcium dynamics in iPSC-derived human neurons. 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.
Publisher
Cold Spring Harbor Laboratory
Reference125 articles.
1. Lechan, R.M. , and Toni, R. (2000). Functional Anatomy of the Hypothalamus and Pituitary. In Endotext, K.R. Feingold, B. Anawalt, A. Boyce, G. Chrousos, W.W. de Herder, K. Dhatariya, K. Dungan, A. Grossman, J.M. Hershman, J. Hofland , et al., eds.
2. Hypothalamic circuits regulating appetite and energy homeostasis: pathways to obesity
3. Monogenic Obesity Syndromes Provide Insights Into the Hypothalamic Regulation of Appetite and Associated Behaviors
4. Parallel, Redundant Circuit Organization for Homeostatic Control of Feeding Behavior
5. Long-Term Efficacy and Safety of Anti-Obesity Treatment: Where Do We Stand?