High Intensity Interval Training Ameliorates Mitochondrial Dysfunction in the Left Ventricle of Mice with Type 2 Diabetes
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) I + II, 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 (PGC1α1 and PGC1α4) 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.
KeywordsMitochondria Exercise training Diabetes Diabetic cardiomyopathy
Late LV filling
Mitochondrial electron transport chain complex (ex. CII = complex II)
Early LV filling
Electron transport chain
High intensity interval training
Mitochondrial calcium uniporter
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha
Peroxisome proliferator-activated receptorγ
Type 2 diabetes mellitus
Mitochondrial transcription factor A
FHB, DC and TOS designed the study, FHB, SS, PC and TOS contributed to data collection. FHB, SS, PC, CM, JS, LHB, MAH, DC, TOS contributed to interpretation of the data and drafting and revising the manuscript.
This work was supported by grants from The Research Council of Norway (FRIPRO Project Number 214458) and (Young Outstanding Investigators Project Number 231764), The Liaison Committee between the Central Norway Regional Health Authority (Project Number 90158300) and UNIKARD (Project Number 217777/H10).
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no competing interests.
The study was approved by the Norwegian council for animal research.
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