期刊
JOURNAL OF MOLECULAR ENDOCRINOLOGY
卷 64, 期 2, 页码 77-90出版社
BIOSCIENTIFICA LTD
DOI: 10.1530/JME-19-0188
关键词
prolactin-releasing peptide; leptin; ob/ob mice; hypothalamic leptin signaling
资金
- GA CR grant of AS CR [18-10591S, RVO:61388963]
- AS CR [RVO:67985823]
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.
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