Prolactin-releasing peptide improved leptin hypothalamic signaling in obese mice. (February 2018)

• Record Type: Journal Article
• Authors: Holubová, Martina; Hrubá, Lucie; Neprašová, Barbora; Majerčíková, Zuzana; Lacinová, Zdeňka; Kuneš, Jaroslav; Maletínská, Lenka; Železná, Blanka
• Is Part Of: Journal of molecular endocrinology. Volume 60:Number 2(2018)
• Page Start: 85
• Page End: 94
• Publication Date: 2018-02
• Subjects: prolactin-releasing peptide -- FOSB -- leptin signaling -- apoptotic activation -- diet-induced obese mice; Molecular endocrinology -- Periodicals; Endocrinology -- Periodicals; 616.407
• DOI: 10.1530/JME-17-0171
• Languages: English
• ISSNs: 0952-5041

Abstract

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-Lys 11 ] prolactin-releasing peptide 31 (palm 11 -PrRP31) in mice with diet-induced obesity (DIO from consuming a high-fat diet) after 28 days of treatment (palm 11 -PrRP31 group) and after 14 days of peptide treatment followed by 14 days of discontinuation (palm 11 -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 palm 11 -PrRP31 group and the palm 11 -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 palm 11 -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 palm 11 -PrRP31-treated groups. This study demonstrates that palm 11 -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.