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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F22%3A00557861" target="_blank" >RIV/61388963:_____/22:00557861 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/67985823:_____/22:00557789 RIV/00216208:11110/22:10444951

Výsledek na webu

<a href="https://doi.org/10.1038/s41387-022-00205-3" target="_blank" >https://doi.org/10.1038/s41387-022-00205-3</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41387-022-00205-3" target="_blank" >10.1038/s41387-022-00205-3</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30105 - Physiology (including cytology)

Projekt

<a href="/cs/project/GA20-00546S" target="_blank" >GA20-00546S: Souvislost obezity, diabetu a neurodegenerace: nový terapeutický potenciál analogů peptidu uvolňujícího prolaktin</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

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

Název periodika

Nutrition & Diabetes

ISSN

2044-4052

e-ISSN

2044-4052

Svazek periodika

12

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

10

Strana od-do

26

Kód UT WoS článku

000798041700001

EID výsledku v databázi Scopus

2-s2.0-85130327429