Prolactin-releasing peptide improved leptin hypothalamic signaling in obese mice.

Abstract

The situation following anti-obesity drug termination is rarely investigated, eventhough a decrease in body weight needs to be sustained. Therefore, this study examined the impact of twice-daily peripheral administration of 5 mg/kg [N-palm-γGlu-Lys11] prolactin-releasing peptide 31 (palm11-PrRP31) in mice with diet-induced obesity (DIO from consuming a high-fat diet) after 28 days of treatment (palm11-PrRP31 group) and after 14 days of peptide treatment followed by 14 days of discontinuation (palm11-PrRP31 + saline group). At the end of the treatment, cumulative food intake, body weight and subcutaneous fat weight/body weight ratio and leptin plasma level were reduced significantly in both the palm11-PrRP31 group and the palm11-PrRP31 + saline group compared to the saline control group. This reduction correlated with significantly increased FOSB, a marker of long-term neuronal potentiation, in the nucleus arcuatus and nucleus tractus solitarii, areas known to be affected by the anorexigenic effect of palm11-PrRP31. Moreover, activation of leptin-related hypothalamic signaling was registered through an increase in phosphoinositide-3-kinase, increased phosphorylation of protein kinase B (PKB, AKT) and enhanced extracellular signal-regulated kinase 1/2 phosphorylation. Besides, lowered apoptotic markers c-JUN N-terminal kinase and c-JUN phosphorylation were registered in the hypothalami of both palm11-PrRP31-treated groups. This study demonstrates that palm11-PrRP31 positively affects feeding and leptin-related hypothalamic signaling, not only after 28 days of treatment but even 14 days after the termination of a 14-day long treatment without the yo-yo effect.

• Authors: Martina Holubová, Lucie Hrubá, Barbora Neprašová, Zuzana Majerčíková, Zdeňka Lacinová, Jaroslav Kuneš, Lenka Maletínská, Blanka Železná
• Journal: Journal of molecular endocrinology (J Mol Endocrinol) Vol. 60 Issue 2 Pg. 85-94 (02 2018) ISSN: 1479-6813 [Electronic] England
• PMID: 29233862 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 Society for Endocrinology.

Chemical References

• Leptin
• Prolactin-Releasing Hormone
• RNA, Messenger
• Receptors, Leptin

Topics

• Animals
• Apoptosis
• Eating
• Fasting (blood)
• Humans
• Hypothalamus (metabolism)
• Leptin (metabolism)
• Male
• Mice, Inbred C57BL
• Mice, Obese
• Neurons (metabolism)
• Organ Size
• Phosphorylation
• Prolactin-Releasing Hormone (metabolism)
• RNA, Messenger (genetics, metabolism)
• Receptors, Leptin (metabolism)
• Signal Transduction