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Lefranc 2021 Int J Mol Sci

From Bioblast
Publications in the MiPMap
Lefranc C, Friederich-Persson M, Foufelle F, Nguyen Dinh Cat A, Jaisser F (2021) Adipocyte-mineralocorticoid receptor alters mitochondrial quality control leading to mitochondrial dysfunction and senescence of visceral adipose tissue. Int J Mol Sci 22:2881.

Β» PMID: 33809055 Open Access

Lefranc Clara, Friederich-Persson Malou, Foufelle Fabienne, Nguyen Dinh Cat Aurelie, Jaisser Frederic (2021) Int J Mol Sci

Abstract: 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. β€’ Keywords: Adipose tissue, Metabolic syndrome, Mineralocorticoid receptor, Mitochondrial dysfunction, Oxidative stress, Senescence β€’ Bioblast editor: Reiswig R β€’ O2k-Network Lab: SE Uppsala Liss P

Labels: MiParea: Respiration, Genetic knockout;overexpression  Pathology: Obesity 

Organism: Mouse  Tissue;cell: Fat  Preparation: Isolated mitochondria 

Coupling state: LEAK, OXPHOS, ET  Pathway:HRR: Oxygraph-2k