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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F20%3A00521836" target="_blank" >RIV/61388963:_____/20:00521836 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/67985823:_____/20:00523849 RIV/00216208:11110/20:10407143 RIV/00023001:_____/20:00079159

Výsledek na webu

<a href="https://doi.org/10.1530/JME-19-0188" target="_blank" >https://doi.org/10.1530/JME-19-0188</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1530/JME-19-0188" target="_blank" >10.1530/JME-19-0188</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30202 - Endocrinology and metabolism (including diabetes, hormones)

Projekt

<a href="/cs/project/GA18-10591S" target="_blank" >GA18-10591S: Lipidované analogy peptidu uvolňujícího prolaktin jako potenciální antiobezitika: zkoumání mechanizmu účinku</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Molecular Endocrinology

ISSN

0952-5041

e-ISSN

—

Svazek periodika

64

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

14

Strana od-do

77-90

Kód UT WoS článku

000508437300003

EID výsledku v databázi Scopus

2-s2.0-85078684029