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Perinatal Treatment with Leptin, but Not Celastrol, Protects from Metabolically Obese, Normal-Weight Phenotype in Rats

Perinatal nutrition has a well-known influence on obesity susceptibility. We previously demonstrated the protective anti-obesity effects of perinatal leptin administration. Celastrol is a natural compound acting as a leptin sensitizer with anti-obesity effects when administered in adult animals. Her...

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Autores principales: Reynés, Bàrbara, Cifre, Margalida, Palou, Andreu, Oliver, Paula
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9183119/
https://www.ncbi.nlm.nih.gov/pubmed/35684076
http://dx.doi.org/10.3390/nu14112277
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author Reynés, Bàrbara
Cifre, Margalida
Palou, Andreu
Oliver, Paula
author_facet Reynés, Bàrbara
Cifre, Margalida
Palou, Andreu
Oliver, Paula
author_sort Reynés, Bàrbara
collection PubMed
description Perinatal nutrition has a well-known influence on obesity susceptibility. We previously demonstrated the protective anti-obesity effects of perinatal leptin administration. Celastrol is a natural compound acting as a leptin sensitizer with anti-obesity effects when administered in adult animals. Here, we aimed to determine if perinatal treatment with leptin, celastrol, or their combination was able to improve metabolic health in animals fed an isocaloric high-fat (HF) diet. Leptin and/or celastrol or their vehicle were administered orally to rats during the suckling period. After weaning, animals were chronically pair-fed with an HF diet provided isocaloric to the intake of a normal-fat diet by control animals to avoid obesity. Isocaloric HF feeding in vehicle-treated animals resulted in metabolic features characteristic of the metabolically obese, normal-weight (MONW) phenotype, i.e., obesity-related disturbances without increased body weight. Leptin treatment prevented liver fat deposition and insulin resistance, induced greater insulin and leptin signaling capacity, decreased gene expression of orexigenic signals at the hypothalamic level, and induced browning in retroperitoneal adipose tissue. However, celastrol treatment did not provide any protective effect and resulted in greater size of the retroperitoneal adipose depot, higher circulating glucose and insulin levels, and decreased leptin sensitivity capacity in adipose tissue. The co-administration of leptin ameliorated the negative effects of celastrol on the retroperitoneal depot, inducing browning and decreasing its size. In conclusion, the perinatal administration of leptin, but not celastrol, provided protection against the consequences of dietary unbalances leading to an MONW phenotype in adulthood.
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spelling pubmed-91831192022-06-10 Perinatal Treatment with Leptin, but Not Celastrol, Protects from Metabolically Obese, Normal-Weight Phenotype in Rats Reynés, Bàrbara Cifre, Margalida Palou, Andreu Oliver, Paula Nutrients Article Perinatal nutrition has a well-known influence on obesity susceptibility. We previously demonstrated the protective anti-obesity effects of perinatal leptin administration. Celastrol is a natural compound acting as a leptin sensitizer with anti-obesity effects when administered in adult animals. Here, we aimed to determine if perinatal treatment with leptin, celastrol, or their combination was able to improve metabolic health in animals fed an isocaloric high-fat (HF) diet. Leptin and/or celastrol or their vehicle were administered orally to rats during the suckling period. After weaning, animals were chronically pair-fed with an HF diet provided isocaloric to the intake of a normal-fat diet by control animals to avoid obesity. Isocaloric HF feeding in vehicle-treated animals resulted in metabolic features characteristic of the metabolically obese, normal-weight (MONW) phenotype, i.e., obesity-related disturbances without increased body weight. Leptin treatment prevented liver fat deposition and insulin resistance, induced greater insulin and leptin signaling capacity, decreased gene expression of orexigenic signals at the hypothalamic level, and induced browning in retroperitoneal adipose tissue. However, celastrol treatment did not provide any protective effect and resulted in greater size of the retroperitoneal adipose depot, higher circulating glucose and insulin levels, and decreased leptin sensitivity capacity in adipose tissue. The co-administration of leptin ameliorated the negative effects of celastrol on the retroperitoneal depot, inducing browning and decreasing its size. In conclusion, the perinatal administration of leptin, but not celastrol, provided protection against the consequences of dietary unbalances leading to an MONW phenotype in adulthood. MDPI 2022-05-29 /pmc/articles/PMC9183119/ /pubmed/35684076 http://dx.doi.org/10.3390/nu14112277 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Reynés, Bàrbara
Cifre, Margalida
Palou, Andreu
Oliver, Paula
Perinatal Treatment with Leptin, but Not Celastrol, Protects from Metabolically Obese, Normal-Weight Phenotype in Rats
title Perinatal Treatment with Leptin, but Not Celastrol, Protects from Metabolically Obese, Normal-Weight Phenotype in Rats
title_full Perinatal Treatment with Leptin, but Not Celastrol, Protects from Metabolically Obese, Normal-Weight Phenotype in Rats
title_fullStr Perinatal Treatment with Leptin, but Not Celastrol, Protects from Metabolically Obese, Normal-Weight Phenotype in Rats
title_full_unstemmed Perinatal Treatment with Leptin, but Not Celastrol, Protects from Metabolically Obese, Normal-Weight Phenotype in Rats
title_short Perinatal Treatment with Leptin, but Not Celastrol, Protects from Metabolically Obese, Normal-Weight Phenotype in Rats
title_sort perinatal treatment with leptin, but not celastrol, protects from metabolically obese, normal-weight phenotype in rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9183119/
https://www.ncbi.nlm.nih.gov/pubmed/35684076
http://dx.doi.org/10.3390/nu14112277
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