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The role of stable analogs of prolactin-releasing peptide in obesity and hypertension
Neprašová, Barbora
Anorexigenic neuropeptides have the potential to decrease food intake and ameliorate obesity and its complications such as high blood glucose or high blood pressure. However, they are not able to cross the blood-brain barrier after peripheral application. Recently, we have designed and synthesized lipidized analogs of prolactin-releasing peptide (PrRP), which resulted in stabilization of the molecule and allowed us to apply the peptide to the periphery to achieve its central biological effect, as it was demonstrated by increased neuronal activity shown by c-Fos in particular hypothalamus nuclei. The aim of this study was to choose the effective dose in acute food intake experiments and then to characterize the subchronic effect of palmitoylated PrRP analogs in mouse and rat models of obesity and diabetes. Several animal models were used: diet-induced obese (DIO) mice (C57Bl/6J), DIO Sprague-Dawley rats, and two rat models with leptin receptor-deficiency: Zucker diabetic (ZDF) rats and spontaneously hypertensive (SHROB) rats. Consumption of a high-fat diet in DIO mice and rats increased their body weight and blood pressure. Two-week intraperitoneal treatment with palmitoylated PrRP31 lowered the food intake, body weight, and returned the blood pressure to normal levels. This treatment also improved...
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The role of stable analogs of prolactin-releasing peptide in obesity and hypertension
Neprašová, Barbora
Anorexigenic neuropeptides have the potential to decrease food intake and ameliorate obesity and its complications such as high blood glucose or high blood pressure. However, they are not able to cross the blood-brain barrier after peripheral application. Recently, we have designed and synthesized lipidized analogs of prolactin-releasing peptide (PrRP), which resulted in stabilization of the molecule and allowed us to apply the peptide to the periphery to achieve its central biological effect, as it was demonstrated by increased neuronal activity shown by c-Fos in particular hypothalamus nuclei. The aim of this study was to choose the effective dose in acute food intake experiments and then to characterize the subchronic effect of palmitoylated PrRP analogs in mouse and rat models of obesity and diabetes. Several animal models were used: diet-induced obese (DIO) mice (C57Bl/6J), DIO Sprague-Dawley rats, and two rat models with leptin receptor-deficiency: Zucker diabetic (ZDF) rats and spontaneously hypertensive (SHROB) rats. Consumption of a high-fat diet in DIO mice and rats increased their body weight and blood pressure. Two-week intraperitoneal treatment with palmitoylated PrRP31 lowered the food intake, body weight, and returned the blood pressure to normal levels. This treatment also improved...
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The role of stable analogs of prolactin-releasing peptide in obesity and hypertension.
Neprašová, Barbora ; Maletínská, Lenka (advisor) ; Poledne, Rudolf (referee) ; Rossmeisl, Martin (referee)
Anorexigenic neuropeptides have the potential to decrease food intake and ameliorate obesity and its complications such as high blood glucose or high blood pressure. However, they are not able to cross the blood-brain barrier after peripheral application. Recently, we have designed and synthesized lipidized analogs of prolactin-releasing peptide (PrRP), which resulted in stabilization of the molecule and allowed us to apply the peptide to the periphery to achieve its central biological effect, as it was demonstrated by increased neuronal activity shown by c-Fos in particular hypothalamus nuclei. The aim of this study was to choose the effective dose in acute food intake experiments and then to characterize the subchronic effect of palmitoylated PrRP analogs in mouse and rat models of obesity and diabetes. Several animal models were used: diet-induced obese (DIO) mice (C57Bl/6J), DIO Sprague-Dawley rats, and two rat models with leptin receptor-deficiency: Zucker diabetic (ZDF) rats and spontaneously hypertensive (SHROB) rats. Consumption of a high-fat diet in DIO mice and rats increased their body weight and blood pressure. Two-week intraperitoneal treatment with palmitoylated PrRP31 lowered the food intake, body weight, and returned the blood pressure to normal levels. This treatment also improved...
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