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...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2017-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-02885-9 |
| _version_ | 1818835112233533440 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T02:45:32Z |
| format | Article |
| id | doaj.art-b3abd049ed6f4508bafbd0af443ec779 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T02:45:32Z |
| publishDate | 2017-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-b3abd049ed6f4508bafbd0af443ec7792022-12-21T20:38:54ZengNature PortfolioScientific Reports2045-23222017-06-017111610.1038/s41598-017-02885-9Adipose tissue dysfunction as a central mechanism leading to dysmetabolic obesity triggered by chronic exposure to p,p’-DDEDiogo Pestana0Diana Teixeira1Manuela Meireles2Cláudia Marques3Sónia Norberto4Carla Sá5Virgínia C. Fernandes6Luísa Correia-Sá7Ana Faria8Luísa Guardão9João T. Guimarães10Wendy N. Cooper11Ionel Sandovici12Valentina F. Domingues13Cristina Delerue-Matos14Rosário Monteiro15Miguel Constância16Conceição Calhau17CINTESIS - Center for Health Technology and Services ResearchCINTESIS - Center for Health Technology and Services ResearchDepartment of Biochemistry, Faculty of Medicine, University of PortoCINTESIS - Center for Health Technology and Services ResearchDepartment of Biochemistry, Faculty of Medicine, University of PortoDepartment of Biochemistry, Faculty of Medicine, University of PortoREQUIMTE/LAQV, Instituto Superior de Engenharia, Instituto Politécnico do PortoREQUIMTE/LAQV, Instituto Superior de Engenharia, Instituto Politécnico do PortoCINTESIS - Center for Health Technology and Services ResearchAnimal House Department, Faculty of Medicine, University of PortoDepartment of Biochemistry, Faculty of Medicine, University of PortoUniversity of Cambridge, Metabolic Research Laboratories, MRC Metabolic Diseases Unit, Department of Obstetrics & Gynaecology and National Institute for Health Research, Cambridge Biomedical Research CentreUniversity of Cambridge, Metabolic Research Laboratories, MRC Metabolic Diseases Unit, Department of Obstetrics & Gynaecology and National Institute for Health Research, Cambridge Biomedical Research CentreREQUIMTE/LAQV, Instituto Superior de Engenharia, Instituto Politécnico do PortoREQUIMTE/LAQV, Instituto Superior de Engenharia, Instituto Politécnico do PortoDepartment of Biochemistry, Faculty of Medicine, University of PortoUniversity of Cambridge, Metabolic Research Laboratories, MRC Metabolic Diseases Unit, Department of Obstetrics & Gynaecology and National Institute for Health Research, Cambridge Biomedical Research CentreCINTESIS - Center for Health Technology and Services ResearchAbstract 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.https://doi.org/10.1038/s41598-017-02885-9 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-017-02885-9 |
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