Synergistic effect of leptin and lipidized PrRP on metabolic pathways in ob/ob mice. (February 2020)

• Record Type: Journal Article
• Authors: Kořínková, Lucia; Holubová, Martina; Neprašová, Barbora; Hrubá, Lucie; Pražienková, Veronika; Bencze, Michal; Haluzík, Martin; Kuneš, Jaroslav; Maletínská, Lenka; Železná, Blanka
• Is Part Of: Journal of molecular endocrinology. Volume 64:Number 2(2020)
• Page Start: 77
• Page End: 90
• Publication Date: 2020-02
• Subjects: prolactin-releasing peptide -- leptin -- ob/ob mice -- hypothalamic leptin signaling; Molecular endocrinology -- Periodicals; Endocrinology -- Periodicals; 616.407
• DOI: 10.1530/JME-19-0188
• Languages: English
• ISSNs: 0952-5041

Abstract

Abstract : Lack of leptin production in ob/ob mice results in obesity and prediabetes that could be partly reversed by leptin supplementation. In the hypothalamus, leptin supports the production of prolactin-releasing peptide (PrRP), an anorexigenic neuropeptide synthesized and active in the brain. In our recent studies, the palmitoylated PrRP analog palm 11 -PrRP31 showed a central anorexigenic effect after peripheral administration. This study investigates whether PrRP could compensate for the deficient leptin in ob/ob mice. In two separate experiments, palm 11 -PrRP31 (5 mg/kg) and leptin (5 or 10 μg/kg) were administered subcutaneously twice daily for 2 or 8 weeks to 8- (younger) or 16-(older) week-old ob/ob mice, respectively, either separately or in combination. The body weight decreasing effect of palm 11 -PrRP31 in both younger and older ob/ob mice was significantly powered by a subthreshold leptin dose, the combined effect could be then considered synergistic. Leptin and palm 11 -PrRP31 also synergistically lowered liver weight and blood glucose in younger ob/ob mice. Reduced liver weight was linked to decreased mRNA expression of lipogenic enzymes. In the hypothalamus of older ob/ob mice, two main leptin anorexigenic signaling pathways, namely, Janus kinase, signal transducer and activator of transcription-3 activation and AMP-activated protein kinase de-activation, were induced by leptin, palm 11 -PrRP31, and their combination. Thus, palm 11 -PrRP31 could partially compensate for leptin deficiency in ob/ob mice. In conclusion, the results demonstrate a synergistic effect of leptin and our lipidized palm 11 -PrRP31 analog.