Baekkerud 2019 Cardiovasc Toxicol
Bækkerud FH, Salerno S, Ceriotti P, Morland C, Storm-Mathisen J, Bergersen LH, Høydal MA, Catalucci D, Stølen TO (2019) High intensity interval training ameliorates mitochondrial dysfunction in the left ventricle of mice with type 2 diabetes. Cardiovasc Toxicol 19:422-31. |
Baekkerud FH, Salerno S, Ceriotti P, Morland C, Storm-Mathisen J, Bergersen LH, Hoeydal MA, Catalucci D, Stoelen TO (2019) Cardiovasc Toxicol
Abstract: Both human and animal studies have shown mitochondrial and contractile dysfunction in hearts of type 2 diabetes mellitus (T2DM). Exercise training has shown positive effects on cardiac function, but its effect on the mitochondria have been insufficiently explored. The aim of this study was to assess the effect of exercise training on mitochondrial function in T2DM hearts. We divided T2DM mice (db/db) into a sedentary and an interval training group at 8 weeks of age and used heterozygote db/+ as controls. After 8 weeks of training, we evaluated mitochondrial structure and function, as well as the levels of mRNA and proteins involved in key metabolic processes from the left ventricle. db/db animals showed decreased oxidative phosphorylation capacity and fragmented mitochondria. Mitochondrial respiration showed a blunted response to Ca2+ along with reduced protein levels of the mitochondrial calcium uniporter. Exercise training ameliorated the reduced oxidative phosphorylation in complex (C) Iβ+βII, CII and CIV, but not CI or Ca2+ response. Mitochondrial fragmentation was partially restored. mRNA levels of isocitrate, succinate and oxoglutarate dehydrogenase were increased in db/db mice and normalized by exercise training. Exercise training induced an upregulation of two transcripts of peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC1Ξ±1 and PGC1Ξ±4) previously linked to endurance training adaptations and strength training adaptations, respectively. The T2DM heart showed mitochondrial dysfunction at multiple levels and exercise training ameliorated some, but not all mitochondrial dysfunctions. β’ Keywords: Diabetes, Diabetic cardiomyopathy, Exercise training, Mitochondria β’ Bioblast editor: Plangger M β’ O2k-Network Lab: NO Trondheim Rognmo O
Labels: MiParea: Respiration, Exercise physiology;nutrition;life style
Pathology: Diabetes
Organism: Mouse Tissue;cell: Heart Preparation: Permeabilized tissue
Coupling state: LEAK, OXPHOS
Pathway: N, S, CIV, NS, ROX
HRR: Oxygraph-2k
Labels, 2019-04