Lipidized Prolactin-Releasing Peptide as a New Potential Tool to Treat Obesity and Type 2 Diabetes Mellitus: Preclinical Studies in Rodent Models

Obesity and type 2 diabetes mellitus (T2DM) are preconditions for the development of metabolic syndrome, which is reaching pandemic levels worldwide, but there are still only a few anti-obesity drugs available. One of the promising tools for the treatment of obesity and related metabolic complicatio...

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Autores principales:	Lucia Mráziková, Barbora Neprašová, Anna Mengr, Andrea Popelová, Veronika Strnadová, Lucie Holá, Blanka Železná, Jaroslav Kuneš, Lenka Maletínská
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	prolactin-releasing peptide rodent models obesity type 2 diabetes leptin resistance Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/3912e19852a7429d857bae0d25a4764e
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spelling	oai:doaj.org-article:3912e19852a7429d857bae0d25a4764e2021-11-18T09:43:42ZLipidized Prolactin-Releasing Peptide as a New Potential Tool to Treat Obesity and Type 2 Diabetes Mellitus: Preclinical Studies in Rodent Models1663-981210.3389/fphar.2021.779962https://doaj.org/article/3912e19852a7429d857bae0d25a4764e2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.779962/fullhttps://doaj.org/toc/1663-9812Obesity and type 2 diabetes mellitus (T2DM) are preconditions for the development of metabolic syndrome, which is reaching pandemic levels worldwide, but there are still only a few anti-obesity drugs available. One of the promising tools for the treatment of obesity and related metabolic complications is anorexigenic peptides, such as prolactin-releasing peptide (PrRP). PrRP is a centrally acting neuropeptide involved in food intake and body weight (BW) regulation. In its natural form, it has limitations for peripheral administration; thus, we designed analogs of PrRP lipidized at the N-terminal region that showed high binding affinities, increased stability and central anorexigenic effects after peripheral administration. In this review, we summarize the preclinical results of our chronic studies on the pharmacological role of the two most potent palmitoylated PrRP31 analogs in various mouse and rat models of obesity, glucose intolerance, and insulin resistance. We used mice and rats with diet-induced obesity fed a high-fat diet, which is considered to simulate the most common form of human obesity, or rodent models with leptin deficiency or disrupted leptin signaling in which long-term food intake regulation by leptin is distorted. The rodent models described in this review are models of metabolic syndrome with different severities, such as obesity or morbid obesity, prediabetes or diabetes and hypertension. We found that the effects of palmitoylated PrRP31 on food intake and BW but not on glucose intolerance require intact leptin signaling. Thus, palmitoylated PrRP31 analogs have potential as therapeutics for obesity and related metabolic complications.Lucia MrázikováBarbora NeprašováBarbora NeprašováAnna MengrAndrea PopelováVeronika StrnadováLucie HoláBlanka ŽeleznáJaroslav KunešJaroslav KunešLenka MaletínskáFrontiers Media S.A.articleprolactin-releasing peptiderodent modelsobesitytype 2 diabetesleptin resistanceTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	prolactin-releasing peptide rodent models obesity type 2 diabetes leptin resistance Therapeutics. Pharmacology RM1-950
spellingShingle	prolactin-releasing peptide rodent models obesity type 2 diabetes leptin resistance Therapeutics. Pharmacology RM1-950 Lucia Mráziková Barbora Neprašová Barbora Neprašová Anna Mengr Andrea Popelová Veronika Strnadová Lucie Holá Blanka Železná Jaroslav Kuneš Jaroslav Kuneš Lenka Maletínská Lipidized Prolactin-Releasing Peptide as a New Potential Tool to Treat Obesity and Type 2 Diabetes Mellitus: Preclinical Studies in Rodent Models
description	Obesity and type 2 diabetes mellitus (T2DM) are preconditions for the development of metabolic syndrome, which is reaching pandemic levels worldwide, but there are still only a few anti-obesity drugs available. One of the promising tools for the treatment of obesity and related metabolic complications is anorexigenic peptides, such as prolactin-releasing peptide (PrRP). PrRP is a centrally acting neuropeptide involved in food intake and body weight (BW) regulation. In its natural form, it has limitations for peripheral administration; thus, we designed analogs of PrRP lipidized at the N-terminal region that showed high binding affinities, increased stability and central anorexigenic effects after peripheral administration. In this review, we summarize the preclinical results of our chronic studies on the pharmacological role of the two most potent palmitoylated PrRP31 analogs in various mouse and rat models of obesity, glucose intolerance, and insulin resistance. We used mice and rats with diet-induced obesity fed a high-fat diet, which is considered to simulate the most common form of human obesity, or rodent models with leptin deficiency or disrupted leptin signaling in which long-term food intake regulation by leptin is distorted. The rodent models described in this review are models of metabolic syndrome with different severities, such as obesity or morbid obesity, prediabetes or diabetes and hypertension. We found that the effects of palmitoylated PrRP31 on food intake and BW but not on glucose intolerance require intact leptin signaling. Thus, palmitoylated PrRP31 analogs have potential as therapeutics for obesity and related metabolic complications.
format	article
author	Lucia Mráziková Barbora Neprašová Barbora Neprašová Anna Mengr Andrea Popelová Veronika Strnadová Lucie Holá Blanka Železná Jaroslav Kuneš Jaroslav Kuneš Lenka Maletínská
author_facet	Lucia Mráziková Barbora Neprašová Barbora Neprašová Anna Mengr Andrea Popelová Veronika Strnadová Lucie Holá Blanka Železná Jaroslav Kuneš Jaroslav Kuneš Lenka Maletínská
author_sort	Lucia Mráziková
title	Lipidized Prolactin-Releasing Peptide as a New Potential Tool to Treat Obesity and Type 2 Diabetes Mellitus: Preclinical Studies in Rodent Models
title_short	Lipidized Prolactin-Releasing Peptide as a New Potential Tool to Treat Obesity and Type 2 Diabetes Mellitus: Preclinical Studies in Rodent Models
title_full	Lipidized Prolactin-Releasing Peptide as a New Potential Tool to Treat Obesity and Type 2 Diabetes Mellitus: Preclinical Studies in Rodent Models
title_fullStr	Lipidized Prolactin-Releasing Peptide as a New Potential Tool to Treat Obesity and Type 2 Diabetes Mellitus: Preclinical Studies in Rodent Models
title_full_unstemmed	Lipidized Prolactin-Releasing Peptide as a New Potential Tool to Treat Obesity and Type 2 Diabetes Mellitus: Preclinical Studies in Rodent Models
title_sort	lipidized prolactin-releasing peptide as a new potential tool to treat obesity and type 2 diabetes mellitus: preclinical studies in rodent models
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/3912e19852a7429d857bae0d25a4764e
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Lipidized Prolactin-Releasing Peptide as a New Potential Tool to Treat Obesity and Type 2 Diabetes Mellitus: Preclinical Studies in Rodent Models

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