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

Mráziková, Lucia ; Hojná, Silvie ; Vaculová, Petra ; Strnad, Štěpán ; Vrkoslav, Vladimír ; Pelantová, Helena ; Kuzma, Marek ; Železná, Blanka ; Kuneš, Jaroslav ; Maletínská, Lenka

Nutrients, 2023-01, Vol.15 (2), p.280 [Periódico revisado por pares]

Switzerland: MDPI AG

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Título:
Lipidized PrRP Analog Exhibits Strong Anti-Obesity and Antidiabetic Properties in Old WKY Rats with Obesity and Glucose Intolerance
Autor: Mráziková, Lucia ; Hojná, Silvie ; Vaculová, Petra ; Strnad, Štěpán ; Vrkoslav, Vladimír ; Pelantová, Helena ; Kuzma, Marek ; Železná, Blanka ; Kuneš, Jaroslav ; Maletínská, Lenka
Assuntos: Animals ; Antidiabetics ; Attenuation ; Body fat ; Brain ; Carbohydrates ; Cholesterol ; Complications ; Diabetes mellitus ; Diet ; Diet, High-Fat - adverse effects ; diet-induced obesity ; Fatty liver ; Gliosis ; Glucagon ; Glucose ; glucose intolerance ; Glucose Intolerance - drug therapy ; Glucose tolerance ; High fat diet ; Histology ; Hypoglycemic Agents - pharmacology ; Hypoglycemic Agents - therapeutic use ; Inflammation ; Insulin ; Insulin Resistance ; Intolerance ; Laboratory animals ; lipid metabolism ; Lipids ; Lipogenesis ; liraglutide ; Liraglutide - pharmacology ; Liraglutide - therapeutic use ; Liver ; Metabolomics ; Mice ; Obesity ; Obesity - drug therapy ; Peptides ; Plasma ; Prediabetic State - drug therapy ; Prolactin ; Prolactin-Releasing Hormone - pharmacology ; Prolactin-releasing peptide ; Proteins ; Rats ; Rats, Inbred WKY ; Steatosis ; Triglycerides ; Urine ; Wistar Kyoto rats
É parte de: Nutrients, 2023-01, Vol.15 (2), p.280
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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These authors contributed equally to this work.
Descrição: 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 (palm -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 palm -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 palm -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 palm -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 palm -PrRP31 and liraglutide in both the periphery and brain.
Editor: Switzerland: MDPI AG
Idioma: Inglês

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

Mráziková, Lucia ; Hojná, Silvie ; Vaculová, Petra ; Strnad, Štěpán ; Vrkoslav, Vladimír ; Pelantová, Helena ; Kuzma, Marek ; Železná, Blanka ; Kuneš, Jaroslav ; Maletínská, Lenka

Switzerland: MDPI AG

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