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

Jörgensen, Sara K. M., Karnosová, Alena, Mazzaferro, Simone, Rowley, Oliver, Chen, Hsiao-Jou Cortina, Robbins, Sarah J., Christofides, Sarah, Merkle, Florian T., Maletínská, Lenka and Petrik, David ORCID: https://orcid.org/0000-0003-3026-0770 2024. An analogue of the Prolactin Releasing Peptide reduces obesity and promotes adult neurogenesis. EMBO Reports 25 (1) , pp. 351-377. 10.1038/s44319-023-00016-2

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Publisher:	Wiley
ISSN:	1469-3178
Date of First Compliant Deposit:	4 January 2024
Date of Acceptance:	17 November 2023
Last Modified:	13 Feb 2024 14:39
URI:	https://orca.cardiff.ac.uk/id/eprint/165223

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