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

Result code in 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>

Alternative codes found

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

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30202 - Endocrinology and metabolism (including diabetes, hormones)

Project

<a href="/en/project/GA18-10591S" target="_blank" >GA18-10591S: Lipidized analogs of prolactin-releasing peptide as potential agents for obesity therapy: search for mechanism of action</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2020

Confidentiality

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

Name of the periodical

Journal of Molecular Endocrinology

ISSN

0952-5041

e-ISSN

—

Volume of the periodical

64

Issue of the periodical within the volume

2

Country of publishing house

GB - UNITED KINGDOM

Number of pages

14

Pages from-to

77-90

UT code for WoS article

000508437300003

EID of the result in the Scopus database

2-s2.0-85078684029