Lefranc 2021 Int J Mol Sci
|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.
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. • Keywords: Adipose tissue, Metabolic syndrome, Mineralocorticoid receptor, Mitochondrial dysfunction, Oxidative stress, Senescence • Bioblast editor: Reiswig R • 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: N HRR: Oxygraph-2k