Adipose tissue dysfunction as a central mechanism leading to dysmetabolic obesity triggered by chronic exposure to p,p’-DDE

Abstract Endocrine-disrupting chemicals such as p,p’-dichlorodiphenyldichloroethylene (p,p’-DDE), are bioaccumulated in the adipose tissue (AT) and have been implicated in the obesity and diabetes epidemic. Thus, it is hypothesized that p,p’-DDE exposure could aggravate the harm of an obesogenic con...

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Autores principales:	Diogo Pestana, Diana Teixeira, Manuela Meireles, Cláudia Marques, Sónia Norberto, Carla Sá, Virgínia C. Fernandes, Luísa Correia-Sá, Ana Faria, Luísa Guardão, João T. Guimarães, Wendy N. Cooper, Ionel Sandovici, Valentina F. Domingues, Cristina Delerue-Matos, Rosário Monteiro, Miguel Constância, Conceição Calhau
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b3abd049ed6f4508bafbd0af443ec779
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spelling	oai:doaj.org-article:b3abd049ed6f4508bafbd0af443ec7792021-12-02T15:05:15ZAdipose tissue dysfunction as a central mechanism leading to dysmetabolic obesity triggered by chronic exposure to p,p’-DDE10.1038/s41598-017-02885-92045-2322https://doaj.org/article/b3abd049ed6f4508bafbd0af443ec7792017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02885-9https://doaj.org/toc/2045-2322Abstract Endocrine-disrupting chemicals such as p,p’-dichlorodiphenyldichloroethylene (p,p’-DDE), are bioaccumulated in the adipose tissue (AT) and have been implicated in the obesity and diabetes epidemic. Thus, it is hypothesized that p,p’-DDE exposure could aggravate the harm of an obesogenic context. We explored the effects of 12 weeks exposure in male Wistar rats’ metabolism and AT biology, assessing a range of metabolic, biochemical and histological parameters. p,p’-DDE -treatment exacerbated several of the metabolic syndrome-accompanying features induced by high-fat diet (HF), such as dyslipidaemia, glucose intolerance and hypertension. A transcriptome analysis comparing mesenteric visceral AT (vAT) of HF and HF/DDE groups revealed a decrease in expression of nervous system and tissue development-related genes, with special relevance for the neuropeptide galanin that also revealed DNA methylation changes at its promoter region. Additionally, we observed an increase in transcription of dipeptidylpeptidase 4, as well as a plasmatic increase of the pro-inflammatory cytokine IL-1β. Our results suggest that p,p’-DDE impairs vAT normal function and effectively decreases the dynamic response to energy surplus. We conclude that p,p’-DDE does not merely accumulate in fat, but may contribute significantly to the development of metabolic dysfunction and inflammation. Our findings reinforce their recognition as metabolism disrupting chemicals, even in non-obesogenic contexts.Diogo PestanaDiana TeixeiraManuela MeirelesCláudia MarquesSónia NorbertoCarla SáVirgínia C. FernandesLuísa Correia-SáAna FariaLuísa GuardãoJoão T. GuimarãesWendy N. CooperIonel SandoviciValentina F. DominguesCristina Delerue-MatosRosário MonteiroMiguel ConstânciaConceição CalhauNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Diogo Pestana Diana Teixeira Manuela Meireles Cláudia Marques Sónia Norberto Carla Sá Virgínia C. Fernandes Luísa Correia-Sá Ana Faria Luísa Guardão João T. Guimarães Wendy N. Cooper Ionel Sandovici Valentina F. Domingues Cristina Delerue-Matos Rosário Monteiro Miguel Constância Conceição Calhau Adipose tissue dysfunction as a central mechanism leading to dysmetabolic obesity triggered by chronic exposure to p,p’-DDE
description	Abstract Endocrine-disrupting chemicals such as p,p’-dichlorodiphenyldichloroethylene (p,p’-DDE), are bioaccumulated in the adipose tissue (AT) and have been implicated in the obesity and diabetes epidemic. Thus, it is hypothesized that p,p’-DDE exposure could aggravate the harm of an obesogenic context. We explored the effects of 12 weeks exposure in male Wistar rats’ metabolism and AT biology, assessing a range of metabolic, biochemical and histological parameters. p,p’-DDE -treatment exacerbated several of the metabolic syndrome-accompanying features induced by high-fat diet (HF), such as dyslipidaemia, glucose intolerance and hypertension. A transcriptome analysis comparing mesenteric visceral AT (vAT) of HF and HF/DDE groups revealed a decrease in expression of nervous system and tissue development-related genes, with special relevance for the neuropeptide galanin that also revealed DNA methylation changes at its promoter region. Additionally, we observed an increase in transcription of dipeptidylpeptidase 4, as well as a plasmatic increase of the pro-inflammatory cytokine IL-1β. Our results suggest that p,p’-DDE impairs vAT normal function and effectively decreases the dynamic response to energy surplus. We conclude that p,p’-DDE does not merely accumulate in fat, but may contribute significantly to the development of metabolic dysfunction and inflammation. Our findings reinforce their recognition as metabolism disrupting chemicals, even in non-obesogenic contexts.
format	article
author	Diogo Pestana Diana Teixeira Manuela Meireles Cláudia Marques Sónia Norberto Carla Sá Virgínia C. Fernandes Luísa Correia-Sá Ana Faria Luísa Guardão João T. Guimarães Wendy N. Cooper Ionel Sandovici Valentina F. Domingues Cristina Delerue-Matos Rosário Monteiro Miguel Constância Conceição Calhau
author_facet	Diogo Pestana Diana Teixeira Manuela Meireles Cláudia Marques Sónia Norberto Carla Sá Virgínia C. Fernandes Luísa Correia-Sá Ana Faria Luísa Guardão João T. Guimarães Wendy N. Cooper Ionel Sandovici Valentina F. Domingues Cristina Delerue-Matos Rosário Monteiro Miguel Constância Conceição Calhau
author_sort	Diogo Pestana
title	Adipose tissue dysfunction as a central mechanism leading to dysmetabolic obesity triggered by chronic exposure to p,p’-DDE
title_short	Adipose tissue dysfunction as a central mechanism leading to dysmetabolic obesity triggered by chronic exposure to p,p’-DDE
title_full	Adipose tissue dysfunction as a central mechanism leading to dysmetabolic obesity triggered by chronic exposure to p,p’-DDE
title_fullStr	Adipose tissue dysfunction as a central mechanism leading to dysmetabolic obesity triggered by chronic exposure to p,p’-DDE
title_full_unstemmed	Adipose tissue dysfunction as a central mechanism leading to dysmetabolic obesity triggered by chronic exposure to p,p’-DDE
title_sort	adipose tissue dysfunction as a central mechanism leading to dysmetabolic obesity triggered by chronic exposure to p,p’-dde
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/b3abd049ed6f4508bafbd0af443ec779
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Adipose tissue dysfunction as a central mechanism leading to dysmetabolic obesity triggered by chronic exposure to p,p’-DDE

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