GPS2 Deficiency Triggers Maladaptive White Adipose Tissue Expansion in Obesity via HIF1A Activation
Summary: Hypertrophic white adipose tissue (WAT) represents a maladaptive mechanism linked to the risk for developing type 2 diabetes in humans. However, the molecular events that predispose WAT to hypertrophy are poorly defined. Here, we demonstrate that adipocyte hypertrophy is triggered by loss o...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2018-09-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718313032 |
| _version_ | 1819289608221884416 |
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| author | Karima Drareni Raphaëlle Ballaire Serena Barilla Mano J. Mathew Amine Toubal Rongrong Fan Ning Liang Catherine Chollet Zhiqiang Huang Maria Kondili Fabienne Foufelle Antoine Soprani Ronan Roussel Jean-François Gautier Fawaz Alzaid Eckardt Treuter Nicolas Venteclef |
| author_facet | Karima Drareni Raphaëlle Ballaire Serena Barilla Mano J. Mathew Amine Toubal Rongrong Fan Ning Liang Catherine Chollet Zhiqiang Huang Maria Kondili Fabienne Foufelle Antoine Soprani Ronan Roussel Jean-François Gautier Fawaz Alzaid Eckardt Treuter Nicolas Venteclef |
| author_sort | Karima Drareni |
| collection | DOAJ |
| description | Summary: Hypertrophic white adipose tissue (WAT) represents a maladaptive mechanism linked to the risk for developing type 2 diabetes in humans. However, the molecular events that predispose WAT to hypertrophy are poorly defined. Here, we demonstrate that adipocyte hypertrophy is triggered by loss of the corepressor GPS2 during obesity. Adipocyte-specific GPS2 deficiency in mice (GPS2 AKO) causes adipocyte hypertrophy, inflammation, and mitochondrial dysfunction during surplus energy. This phenotype is driven by HIF1A activation that orchestrates inadequate WAT remodeling and disrupts mitochondrial activity, which can be reversed by pharmacological or genetic HIF1A inhibition. Correlation analysis of gene expression in human adipose tissue reveals a negative relationship between GPS2 and HIF1A, adipocyte hypertrophy, and insulin resistance. We propose therefore that the obesity-associated loss of GPS2 in adipocytes predisposes for a maladaptive WAT expansion and a pro-diabetic status in mice and humans. : Drareni et al. identify a role for the transcriptional corepressor GPS2 in the regulation of adipocyte hypertrophy. They provide evidence that adipocyte-specific loss of GPS2 predisposes toward maladaptive adipose tissue expansion and pro-diabetic status through activation of HIF1A transcriptional activity. Keywords: corepressor, transcription, adipose tissue, obesity, type 2 diabetes, insulin resistance, GPS2, HIF1A |
| first_indexed | 2024-12-24T03:09:33Z |
| format | Article |
| id | doaj.art-326c110314a9499289414635556a19cd |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-24T03:09:33Z |
| publishDate | 2018-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-326c110314a9499289414635556a19cd2022-12-21T17:17:53ZengElsevierCell Reports2211-12472018-09-01241129572971.e6GPS2 Deficiency Triggers Maladaptive White Adipose Tissue Expansion in Obesity via HIF1A ActivationKarima Drareni0Raphaëlle Ballaire1Serena Barilla2Mano J. Mathew3Amine Toubal4Rongrong Fan5Ning Liang6Catherine Chollet7Zhiqiang Huang8Maria Kondili9Fabienne Foufelle10Antoine Soprani11Ronan Roussel12Jean-François Gautier13Fawaz Alzaid14Eckardt Treuter15Nicolas Venteclef16INSERM, Cordeliers Research Centre, Sorbonne Paris Cité, Université Paris Descartes, Université Paris Diderot, Paris, FranceINSERM, Cordeliers Research Centre, Sorbonne Paris Cité, Université Paris Descartes, Université Paris Diderot, Paris, France; Inovarion, 75013 Paris, FranceKarolinska Institutet, Department of Biosciences and Nutrition, Huddinge, SwedenINSERM, Cordeliers Research Centre, Sorbonne Paris Cité, Université Paris Descartes, Université Paris Diderot, Paris, FranceINSERM, Cordeliers Research Centre, Sorbonne Paris Cité, Université Paris Descartes, Université Paris Diderot, Paris, FranceKarolinska Institutet, Department of Biosciences and Nutrition, Huddinge, SwedenKarolinska Institutet, Department of Biosciences and Nutrition, Huddinge, SwedenINSERM, Cordeliers Research Centre, Sorbonne Paris Cité, Université Paris Descartes, Université Paris Diderot, Paris, FranceKarolinska Institutet, Department of Biosciences and Nutrition, Huddinge, SwedenINSERM, Cordeliers Research Centre, Sorbonne Paris Cité, Université Paris Descartes, Université Paris Diderot, Paris, FranceINSERM, Cordeliers Research Centre, Sorbonne Paris Cité, Université Paris Descartes, Université Paris Diderot, Paris, FranceINSERM, Cordeliers Research Centre, Sorbonne Paris Cité, Université Paris Descartes, Université Paris Diderot, Paris, France; Clinique Geoffroy Saint-Hilaire, Ramsey General de Santé, Paris, FranceINSERM, Cordeliers Research Centre, Sorbonne Paris Cité, Université Paris Descartes, Université Paris Diderot, Paris, France; Diabetology, Endocrinology and Nutrition Department, DHU FIRE, Bichat Hospital, AP-HP, Paris, France; Faculty of Medicine, University Paris-Diderot, Paris, FranceINSERM, Cordeliers Research Centre, Sorbonne Paris Cité, Université Paris Descartes, Université Paris Diderot, Paris, France; Assistance Publique-Hôpitaux de Paris, Lariboisière Hospital, Department of Diabetes, Clinical Investigation Centre (CIC-9504), University Paris-Diderot, Paris, France; Faculty of Medicine, University Paris-Diderot, Paris, FranceINSERM, Cordeliers Research Centre, Sorbonne Paris Cité, Université Paris Descartes, Université Paris Diderot, Paris, FranceKarolinska Institutet, Department of Biosciences and Nutrition, Huddinge, Sweden; Corresponding authorINSERM, Cordeliers Research Centre, Sorbonne Paris Cité, Université Paris Descartes, Université Paris Diderot, Paris, France; Corresponding authorSummary: Hypertrophic white adipose tissue (WAT) represents a maladaptive mechanism linked to the risk for developing type 2 diabetes in humans. However, the molecular events that predispose WAT to hypertrophy are poorly defined. Here, we demonstrate that adipocyte hypertrophy is triggered by loss of the corepressor GPS2 during obesity. Adipocyte-specific GPS2 deficiency in mice (GPS2 AKO) causes adipocyte hypertrophy, inflammation, and mitochondrial dysfunction during surplus energy. This phenotype is driven by HIF1A activation that orchestrates inadequate WAT remodeling and disrupts mitochondrial activity, which can be reversed by pharmacological or genetic HIF1A inhibition. Correlation analysis of gene expression in human adipose tissue reveals a negative relationship between GPS2 and HIF1A, adipocyte hypertrophy, and insulin resistance. We propose therefore that the obesity-associated loss of GPS2 in adipocytes predisposes for a maladaptive WAT expansion and a pro-diabetic status in mice and humans. : Drareni et al. identify a role for the transcriptional corepressor GPS2 in the regulation of adipocyte hypertrophy. They provide evidence that adipocyte-specific loss of GPS2 predisposes toward maladaptive adipose tissue expansion and pro-diabetic status through activation of HIF1A transcriptional activity. Keywords: corepressor, transcription, adipose tissue, obesity, type 2 diabetes, insulin resistance, GPS2, HIF1Ahttp://www.sciencedirect.com/science/article/pii/S2211124718313032 |
| spellingShingle | Karima Drareni Raphaëlle Ballaire Serena Barilla Mano J. Mathew Amine Toubal Rongrong Fan Ning Liang Catherine Chollet Zhiqiang Huang Maria Kondili Fabienne Foufelle Antoine Soprani Ronan Roussel Jean-François Gautier Fawaz Alzaid Eckardt Treuter Nicolas Venteclef GPS2 Deficiency Triggers Maladaptive White Adipose Tissue Expansion in Obesity via HIF1A Activation Cell Reports |
| title | GPS2 Deficiency Triggers Maladaptive White Adipose Tissue Expansion in Obesity via HIF1A Activation |
| title_full | GPS2 Deficiency Triggers Maladaptive White Adipose Tissue Expansion in Obesity via HIF1A Activation |
| title_fullStr | GPS2 Deficiency Triggers Maladaptive White Adipose Tissue Expansion in Obesity via HIF1A Activation |
| title_full_unstemmed | GPS2 Deficiency Triggers Maladaptive White Adipose Tissue Expansion in Obesity via HIF1A Activation |
| title_short | GPS2 Deficiency Triggers Maladaptive White Adipose Tissue Expansion in Obesity via HIF1A Activation |
| title_sort | gps2 deficiency triggers maladaptive white adipose tissue expansion in obesity via hif1a activation |
| url | http://www.sciencedirect.com/science/article/pii/S2211124718313032 |
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