Lipidized PrRP Analog Exhibits Strong Anti-Obesity and Antidiabetic Properties in Old WKY Rats with Obesity and Glucose Intolerance

0568010 - ÚOCHB 2024 RIV CH eng J - Journal Article
Mráziková, Lucia - Hojná, S. - Vaculová, Petra - Strnad, Štěpán - Vrkoslav, Vladimír - Pelantová, Helena - Kuzma, Marek - Železná, Blanka - Kuneš, Jaroslav - Maletínská, Lenka
Lipidized PrRP Analog Exhibits Strong Anti-Obesity and Antidiabetic Properties in Old WKY Rats with Obesity and Glucose Intolerance.
Nutrients. Roč. 15, č. 2 (2023), č. článku 280. E-ISSN 2072-6643
R&D Projects: GA MŠMT(CZ) LX22NPO5104; GA ČR(CZ) GA20-00546S
Institutional support: RVO:61388963 ; RVO:61388971
Keywords : diet-induced obesity * Wistar Kyoto rats * glucose intolerance * prolactin-releasing peptide * liraglutide * lipid metabolism * astrocytosis * lipidomics * metabolomics
OECD category: Physiology (including cytology); Biochemistry and molecular biology (MBU-M)
Impact factor: 5.9, year: 2022
Method of publishing: Open access
https://doi.org/10.3390/nu15020280

Prolactin-releasing peptide (PrRP) is an anorexigenic neuropeptide that has potential for the treatment of obesity and its complications. Recently, we designed a palmitoylated PrRP31 analog (palm11-PrRP31) that is more stable than the natural peptide and able to act centrally after peripheral administration. This analog acted as an anti-obesity and glucose-lowering agent, attenuating lipogenesis in rats and mice with high-fat (HF) diet-induced obesity. In Wistar Kyoto (WKY) rats fed a HF diet for 52 weeks, we explored glucose intolerance, but also prediabetes, liver steatosis and insulin resistance-related changes, as well as neuroinflammation in the brain. A potential beneficial effect of 6 weeks of treatment with palm11-PrRP31 and liraglutide as comparator was investigated. Liver lipid profiles, as well as urinary and plasma metabolomic profiles, were measured by lipidomics and metabolomics, respectively. Old obese WKY rats showed robust glucose intolerance that was attenuated by palm11-PrRP31, but not by liraglutide treatment. On the contrary, liraglutide had a beneficial effect on insulin resistance parameters. Despite obesity and prediabetes, WKY rats did not develop steatosis owing to HF diet feeding, even though liver lipogenesis was enhanced. Plasma triglycerides and cholesterol were not increased by HFD feeding, which points to unincreased lipid transport from the liver. The liver lipid profile was significantly altered by a HF diet that remained unaffected by palm11-PrRP31 or liraglutide treatment. The HF-diet-fed WKY rats revealed astrogliosis in the brain cortex and hippocampus, which was attenuated by treatment. In conclusion, this study suggested multiple beneficial anti-obesity-related effects of palm11-PrRP31 and liraglutide in both the periphery and brain.
Permanent Link: https://hdl.handle.net/11104/0339340