Synergistic effect of leptin and lipidized PrRP on metabolic pathways in ob/ob mice
Language English Country Great Britain, England Media print
Document type Journal Article
PubMed
31855558
DOI
10.1530/jme-19-0188
PII: JME-19-0188.R2
Knihovny.cz E-resources
- Keywords
- hypothalamic leptin signaling, leptin, ob/ob mice, prolactin-releasing peptide,
- MeSH
- Glucose Tolerance Test MeSH
- Prolactin-Releasing Hormone analogs & derivatives chemistry pharmacology therapeutic use MeSH
- Liver drug effects metabolism MeSH
- Leptin pharmacology therapeutic use MeSH
- Metabolic Networks and Pathways drug effects MeSH
- Lipid Metabolism drug effects MeSH
- Mice, Obese MeSH
- Mice MeSH
- Obesity drug therapy metabolism MeSH
- Eating drug effects MeSH
- Drug Synergism MeSH
- Body Weight drug effects MeSH
- Body Temperature MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Prolactin-Releasing Hormone MeSH
- Leptin MeSH
- palm11-PrRP31 MeSH Browser
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 palm11-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, palm11-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 palm11-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 palm11-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, palm11-PrRP31, and their combination. Thus, palm11-PrRP31 could partially compensate for leptin deficiency in ob/ob mice. In conclusion, the results demonstrate a synergistic effect of leptin and our lipidized palm11-PrRP31 analog.
1st Faculty of Medicine Charles University Prague Prague Czech Republic
Institute for Clinical and Experimental Medicine Prague Czech Republic
Institute of Physiology Academy of Sciences of the Czech Republic Prague Czech Republic
References provided by Crossref.org
Lipidization as a tool toward peptide therapeutics
