Synergistic effect of leptin and lipidized PrRP on metabolic pathways in ob/ob mice

0523849 - FGÚ 2021 RIV GB eng J - Článek v odborném periodiku
Kořínková, L. - Holubová, M. - Neprašová, B. - Hrubá, L. - Pražienková, V. - Bencze, Michal - Haluzík, M. - Kuneš, Jaroslav - Maletínská, L. - Železná, B.
Synergistic effect of leptin and lipidized PrRP on metabolic pathways in ob/ob mice.
Journal of Molecular Endocrinology. Roč. 64, č. 2 (2020), s. 77-90. ISSN 0952-5041. E-ISSN 1479-6813
Grant CEP: GA ČR(CZ) GA18-10591S
Institucionální podpora: RVO:67985823
Klíčová slova: prolactin-releasing peptide * leptin * ob/ob mice * hypothalamic leptin signaling
Obor OECD: Endocrinology and metabolism (including diabetes, hormones)
Impakt faktor: 5.098, rok: 2020
Způsob publikování: Open access
https://doi.org/10.1530/JME-19-0188

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 mu g/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.
Trvalý link: http://hdl.handle.net/11104/0308126