Palmitoylated prolactin-releasing peptide treatment had neuroprotective but not anti-obesity effect in fa/fa rats with leptin signaling disturbances.

Autor: Mráziková L; Institute of Organic Chemistry and Biochemistry CAS, Prague, Czech Republic.; First Faculty of Medicine, Charles University, Prague, Czech Republic., Hojná S; Institute of Physiology CAS, Prague, Czech Republic., Pačesová A; Institute of Organic Chemistry and Biochemistry CAS, Prague, Czech Republic., Hrubá L; Institute of Organic Chemistry and Biochemistry CAS, Prague, Czech Republic., Strnadová V; Institute of Organic Chemistry and Biochemistry CAS, Prague, Czech Republic., Neprašová B; Institute of Organic Chemistry and Biochemistry CAS, Prague, Czech Republic.; Institute of Physiology CAS, Prague, Czech Republic., Železná B; Institute of Organic Chemistry and Biochemistry CAS, Prague, Czech Republic., Kuneš J; Institute of Organic Chemistry and Biochemistry CAS, Prague, Czech Republic.; Institute of Physiology CAS, Prague, Czech Republic., Maletínská L; Institute of Organic Chemistry and Biochemistry CAS, Prague, Czech Republic. maletin@uochb.cas.cz.
Jazyk: angličtina
Zdroj: Nutrition & diabetes [Nutr Diabetes] 2022 May 19; Vol. 12 (1), pp. 26. Date of Electronic Publication: 2022 May 19.
DOI: 10.1038/s41387-022-00205-3
Abstrakt: Background/objective: Anorexigenic palmitoylated prolactin-releasing peptide (palm 11 -PrRP) is able to act centrally after peripheral administration in rat and mouse models of obesity, type 2 diabetes mellitus and/or neurodegeneration. Functional leptin and intact leptin signaling pathways are necessary for the body weight reducing and glucose tolerance improving effect of palm 11 -PrRP. We have previously shown that palm 11 -PrRP31 had glucose-lowering properties but not anti-obesity effect in Koletsky rats with leptin signaling disturbances, so improvements in glucose metabolism appear to be completely independent of leptin signaling. The purpose of this study was to describe relationship between metabolic and neurodegenerative pathologies and explore if palm 11 -PrRP31 could ameliorate them in obese fa/fa rat model with leptin signaling disruption.
Subject/methods: The fa/fa rats and their age-matched lean controls at the age 32 weeks were used for this study. The rats were infused for 2 months with saline or palm 11 -PrRP31 (n = 7-8 per group) at a dose of 5 mg/kg per day using Alzet osmotic pumps. During the dosing period food intake and body weight were monitored. At the end of experiment the oral glucose tolerance test was performed; plasma and tissue samples were collected and arterial blood pressure was measured. Then, markers of leptin and insulin signaling, Tau phosphorylation, neuroinflammation, and synaptogenesis were measured by western blotting and immunohistochemistry.
Results: Fa/fa rats developed obesity, mild glucose intolerance, and peripheral insulin resistance but not hypertension while palm 11 -PrRP31 treatment neither lowered body weight nor attenuated glucose tolerance but ameliorated leptin and insulin signaling and synaptogenesis in hippocampus.
Conclusion: We demonstrated that palm 11 -PrRP31 had neuroprotective features without anti-obesity and glucose lowering effects in fa/fa rats. This data suggest that this analog has the potential to exert neuroprotective effect despite of leptin signaling disturbances in this rat model.
(© 2022. The Author(s).)
Databáze: MEDLINE
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