Postnatal Growth after Intrauterine Growth Restriction Alters Central Leptin Signal and Energy Homeostasis

Intrauterine growth restriction (IUGR) is closely linked with metabolic diseases, appetite disorders and obesity at adulthood. Leptin, a major adipokine secreted by adipose tissue, circulates in direct proportion to body fat stores, enters the brain and regulates food intake and energy expenditure....

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Autores principales: Coupé, Bérengère, Grit, Isabelle, Hulin, Philippe, Randuineau, Gwenaëlle, Parnet, Patricia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3264579/
https://www.ncbi.nlm.nih.gov/pubmed/22291999
http://dx.doi.org/10.1371/journal.pone.0030616
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author Coupé, Bérengère
Grit, Isabelle
Hulin, Philippe
Randuineau, Gwenaëlle
Parnet, Patricia
author_facet Coupé, Bérengère
Grit, Isabelle
Hulin, Philippe
Randuineau, Gwenaëlle
Parnet, Patricia
author_sort Coupé, Bérengère
collection PubMed
description Intrauterine growth restriction (IUGR) is closely linked with metabolic diseases, appetite disorders and obesity at adulthood. Leptin, a major adipokine secreted by adipose tissue, circulates in direct proportion to body fat stores, enters the brain and regulates food intake and energy expenditure. Deficient leptin neuronal signalling favours weight gain by affecting central homeostatic circuitry. The aim of this study was to determine if leptin resistance was programmed by perinatal nutritional environment and to decipher potential cellular mechanisms underneath. We clearly demonstrated that 5 months old IUGR rats develop a decrease of leptin sentivity, characterized by no significant reduction of food intake following an intraperitoneal injection of leptin. Apart from the resistance to leptin injection, results obtained from IUGR rats submitted to rapid catch-up growth differed from those of IUGR rats with no catch-up since we observed, for the first group only, fat accumulation, increased appetite for food rich in fat and increased leptin synthesis. Centrally, the leptin resistant state of both groups was associated with a complex and not always similar changes in leptin receptor signalling steps. Leptin resistance in IUGR rats submitted to rapid catch-up was associated with alteration in AKT and mTOR pathways. Alternatively, in IUGR rats with no catch-up, leptin resistance was associated with low hypothalamic expression of LepRa and LepRb. This study reveals leptin resistance as an early marker of metabolic disorders that appears before any evidence of body weight increase in IUGR rats but whose mechanisms could depend of nutritional environment of the perinatal period.
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spelling pubmed-32645792012-01-30 Postnatal Growth after Intrauterine Growth Restriction Alters Central Leptin Signal and Energy Homeostasis Coupé, Bérengère Grit, Isabelle Hulin, Philippe Randuineau, Gwenaëlle Parnet, Patricia PLoS One Research Article Intrauterine growth restriction (IUGR) is closely linked with metabolic diseases, appetite disorders and obesity at adulthood. Leptin, a major adipokine secreted by adipose tissue, circulates in direct proportion to body fat stores, enters the brain and regulates food intake and energy expenditure. Deficient leptin neuronal signalling favours weight gain by affecting central homeostatic circuitry. The aim of this study was to determine if leptin resistance was programmed by perinatal nutritional environment and to decipher potential cellular mechanisms underneath. We clearly demonstrated that 5 months old IUGR rats develop a decrease of leptin sentivity, characterized by no significant reduction of food intake following an intraperitoneal injection of leptin. Apart from the resistance to leptin injection, results obtained from IUGR rats submitted to rapid catch-up growth differed from those of IUGR rats with no catch-up since we observed, for the first group only, fat accumulation, increased appetite for food rich in fat and increased leptin synthesis. Centrally, the leptin resistant state of both groups was associated with a complex and not always similar changes in leptin receptor signalling steps. Leptin resistance in IUGR rats submitted to rapid catch-up was associated with alteration in AKT and mTOR pathways. Alternatively, in IUGR rats with no catch-up, leptin resistance was associated with low hypothalamic expression of LepRa and LepRb. This study reveals leptin resistance as an early marker of metabolic disorders that appears before any evidence of body weight increase in IUGR rats but whose mechanisms could depend of nutritional environment of the perinatal period. Public Library of Science 2012-01-23 /pmc/articles/PMC3264579/ /pubmed/22291999 http://dx.doi.org/10.1371/journal.pone.0030616 Text en Coupé et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Coupé, Bérengère
Grit, Isabelle
Hulin, Philippe
Randuineau, Gwenaëlle
Parnet, Patricia
Postnatal Growth after Intrauterine Growth Restriction Alters Central Leptin Signal and Energy Homeostasis
title Postnatal Growth after Intrauterine Growth Restriction Alters Central Leptin Signal and Energy Homeostasis
title_full Postnatal Growth after Intrauterine Growth Restriction Alters Central Leptin Signal and Energy Homeostasis
title_fullStr Postnatal Growth after Intrauterine Growth Restriction Alters Central Leptin Signal and Energy Homeostasis
title_full_unstemmed Postnatal Growth after Intrauterine Growth Restriction Alters Central Leptin Signal and Energy Homeostasis
title_short Postnatal Growth after Intrauterine Growth Restriction Alters Central Leptin Signal and Energy Homeostasis
title_sort postnatal growth after intrauterine growth restriction alters central leptin signal and energy homeostasis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3264579/
https://www.ncbi.nlm.nih.gov/pubmed/22291999
http://dx.doi.org/10.1371/journal.pone.0030616
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