Adipocyte-Mineralocorticoid Receptor Alters Mitochondrial Quality Control Leading to Mitochondrial Dysfunction and Senescence of Visceral Adipose Tissue
Mineralocorticoid receptor (MR) expression is increased in the adipose tissue (AT) of obese patients and animals. We previously demonstrated that adipocyte-MR overexpression in mice (Adipo-MROE mice) is associated with metabolic alterations. Moreover, we showed that MR regulates mitochondrial dysfun...
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doaj-2daaa66bb1184bd6a45250beb9828e2b2021-03-13T00:02:24ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-03-01222881288110.3390/ijms22062881Adipocyte-Mineralocorticoid Receptor Alters Mitochondrial Quality Control Leading to Mitochondrial Dysfunction and Senescence of Visceral Adipose TissueClara Lefranc0Malou Friederich-Persson1Fabienne Foufelle2Aurélie Nguyen Dinh Cat3Frédéric Jaisser4Centre de Recherche des Cordeliers, Inserm, Sorbonne Université, Université de Paris, Team Metabolic Diseases, Diabetes and Comorbidities, 75006 Paris, FranceDepartment of Medical Cell Biology, Uppsala University, 751 23 Uppsala, SwedenCentre de Recherche des Cordeliers, Inserm, Sorbonne Université, Université de Paris, Team Metabolic Diseases, Diabetes and Comorbidities, 75006 Paris, FranceCentre de Recherche des Cordeliers, Inserm, Sorbonne Université, Université de Paris, Team Metabolic Diseases, Diabetes and Comorbidities, 75006 Paris, FranceCentre de Recherche des Cordeliers, Inserm, Sorbonne Université, Université de Paris, Team Metabolic Diseases, Diabetes and Comorbidities, 75006 Paris, FranceMineralocorticoid receptor (MR) expression is increased in the adipose tissue (AT) of obese patients and animals. We previously demonstrated that adipocyte-MR overexpression in mice (Adipo-MROE mice) is associated with metabolic alterations. Moreover, we showed that MR regulates mitochondrial dysfunction and cellular senescence in the visceral AT of obese db/db mice. Our hypothesis is that adipocyte-MR overactivation triggers mitochondrial dysfunction and cellular senescence, through increased mitochondrial oxidative stress (OS). Using the Adipo-MROE mice with conditional adipocyte-MR expression, we evaluated the specific effects of adipocyte-MR on global and mitochondrial OS, as well as on OS-induced damage. Mitochondrial function was assessed by high throughput respirometry. Molecular mechanisms were probed in AT focusing on mitochondrial quality control and senescence markers. Adipo-MROE mice exhibited increased mitochondrial OS and altered mitochondrial respiration, associated with reduced biogenesis and increased fission. This was associated with OS-induced DNA-damage and AT premature senescence. In conclusion, targeted adipocyte-MR overexpression leads to an imbalance in mitochondrial dynamics and regeneration, to mitochondrial dysfunction and to ageing in visceral AT. These data bring new insights into the MR-dependent AT dysfunction in obesity.https://www.mdpi.com/1422-0067/22/6/2881mineralocorticoid receptormitochondrial dysfunctionadipose tissueoxidative stresssenescencemetabolic syndrome |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Clara Lefranc Malou Friederich-Persson Fabienne Foufelle Aurélie Nguyen Dinh Cat Frédéric Jaisser |
spellingShingle |
Clara Lefranc Malou Friederich-Persson Fabienne Foufelle Aurélie Nguyen Dinh Cat Frédéric Jaisser Adipocyte-Mineralocorticoid Receptor Alters Mitochondrial Quality Control Leading to Mitochondrial Dysfunction and Senescence of Visceral Adipose Tissue International Journal of Molecular Sciences mineralocorticoid receptor mitochondrial dysfunction adipose tissue oxidative stress senescence metabolic syndrome |
author_facet |
Clara Lefranc Malou Friederich-Persson Fabienne Foufelle Aurélie Nguyen Dinh Cat Frédéric Jaisser |
author_sort |
Clara Lefranc |
title |
Adipocyte-Mineralocorticoid Receptor Alters Mitochondrial Quality Control Leading to Mitochondrial Dysfunction and Senescence of Visceral Adipose Tissue |
title_short |
Adipocyte-Mineralocorticoid Receptor Alters Mitochondrial Quality Control Leading to Mitochondrial Dysfunction and Senescence of Visceral Adipose Tissue |
title_full |
Adipocyte-Mineralocorticoid Receptor Alters Mitochondrial Quality Control Leading to Mitochondrial Dysfunction and Senescence of Visceral Adipose Tissue |
title_fullStr |
Adipocyte-Mineralocorticoid Receptor Alters Mitochondrial Quality Control Leading to Mitochondrial Dysfunction and Senescence of Visceral Adipose Tissue |
title_full_unstemmed |
Adipocyte-Mineralocorticoid Receptor Alters Mitochondrial Quality Control Leading to Mitochondrial Dysfunction and Senescence of Visceral Adipose Tissue |
title_sort |
adipocyte-mineralocorticoid receptor alters mitochondrial quality control leading to mitochondrial dysfunction and senescence of visceral adipose tissue |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-03-01 |
description |
Mineralocorticoid receptor (MR) expression is increased in the adipose tissue (AT) of obese patients and animals. We previously demonstrated that adipocyte-MR overexpression in mice (Adipo-MROE mice) is associated with metabolic alterations. Moreover, we showed that MR regulates mitochondrial dysfunction and cellular senescence in the visceral AT of obese db/db mice. Our hypothesis is that adipocyte-MR overactivation triggers mitochondrial dysfunction and cellular senescence, through increased mitochondrial oxidative stress (OS). Using the Adipo-MROE mice with conditional adipocyte-MR expression, we evaluated the specific effects of adipocyte-MR on global and mitochondrial OS, as well as on OS-induced damage. Mitochondrial function was assessed by high throughput respirometry. Molecular mechanisms were probed in AT focusing on mitochondrial quality control and senescence markers. Adipo-MROE mice exhibited increased mitochondrial OS and altered mitochondrial respiration, associated with reduced biogenesis and increased fission. This was associated with OS-induced DNA-damage and AT premature senescence. In conclusion, targeted adipocyte-MR overexpression leads to an imbalance in mitochondrial dynamics and regeneration, to mitochondrial dysfunction and to ageing in visceral AT. These data bring new insights into the MR-dependent AT dysfunction in obesity. |
topic |
mineralocorticoid receptor mitochondrial dysfunction adipose tissue oxidative stress senescence metabolic syndrome |
url |
https://www.mdpi.com/1422-0067/22/6/2881 |
work_keys_str_mv |
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