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

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 nece...

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Autores principales: Mráziková, Lucia, Hojná, Silvie, Pačesová, Andrea, Hrubá, Lucie, Strnadová, Veronika, Neprašová, Barbora, Železná, Blanka, Kuneš, Jaroslav, Maletínská, Lenka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9119973/
https://www.ncbi.nlm.nih.gov/pubmed/35589696
http://dx.doi.org/10.1038/s41387-022-00205-3
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author Mráziková, Lucia
Hojná, Silvie
Pačesová, Andrea
Hrubá, Lucie
Strnadová, Veronika
Neprašová, Barbora
Železná, Blanka
Kuneš, Jaroslav
Maletínská, Lenka
author_facet Mráziková, Lucia
Hojná, Silvie
Pačesová, Andrea
Hrubá, Lucie
Strnadová, Veronika
Neprašová, Barbora
Železná, Blanka
Kuneš, Jaroslav
Maletínská, Lenka
author_sort Mráziková, Lucia
collection PubMed
description 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.
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spelling pubmed-91199732022-05-21 Palmitoylated prolactin-releasing peptide treatment had neuroprotective but not anti-obesity effect in fa/fa rats with leptin signaling disturbances Mráziková, Lucia Hojná, Silvie Pačesová, Andrea Hrubá, Lucie Strnadová, Veronika Neprašová, Barbora Železná, Blanka Kuneš, Jaroslav Maletínská, Lenka Nutr Diabetes Article 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. Nature Publishing Group UK 2022-05-19 /pmc/articles/PMC9119973/ /pubmed/35589696 http://dx.doi.org/10.1038/s41387-022-00205-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Mráziková, Lucia
Hojná, Silvie
Pačesová, Andrea
Hrubá, Lucie
Strnadová, Veronika
Neprašová, Barbora
Železná, Blanka
Kuneš, Jaroslav
Maletínská, Lenka
Palmitoylated prolactin-releasing peptide treatment had neuroprotective but not anti-obesity effect in fa/fa rats with leptin signaling disturbances
title Palmitoylated prolactin-releasing peptide treatment had neuroprotective but not anti-obesity effect in fa/fa rats with leptin signaling disturbances
title_full Palmitoylated prolactin-releasing peptide treatment had neuroprotective but not anti-obesity effect in fa/fa rats with leptin signaling disturbances
title_fullStr Palmitoylated prolactin-releasing peptide treatment had neuroprotective but not anti-obesity effect in fa/fa rats with leptin signaling disturbances
title_full_unstemmed Palmitoylated prolactin-releasing peptide treatment had neuroprotective but not anti-obesity effect in fa/fa rats with leptin signaling disturbances
title_short Palmitoylated prolactin-releasing peptide treatment had neuroprotective but not anti-obesity effect in fa/fa rats with leptin signaling disturbances
title_sort palmitoylated prolactin-releasing peptide treatment had neuroprotective but not anti-obesity effect in fa/fa rats with leptin signaling disturbances
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9119973/
https://www.ncbi.nlm.nih.gov/pubmed/35589696
http://dx.doi.org/10.1038/s41387-022-00205-3
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