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Molecular Biology

Mitochondrial DNA copy number associates with insulin sensitivity and aerobic capacity, and differs between sedentary, overweight middle-aged males with and without type 2 diabetes

International Journal of Obesity volume 44, pages 929–936 (2020)Cite this article

Subjects

Abstract

Background/objectives

Increased risk of type 2 diabetes mellitus (T2DM) is linked to impaired muscle mitochondrial function and reduced mitochondrial DNA copy number (mtDNAnum). However, studies have failed to control for habitual physical activity levels, which directly influences both mtDNA copy number and insulin sensitivity. We, therefore, examined whether physical conditioning status (maximal oxygen uptake, V̇O2max) was associated with skeletal muscle mitochondrial volume and mtDNAnum, and was predictive of T2DM in overweight, middle-aged men.

Methods

Whole-body physiological (ISI—insulin sensitivity index, HOMA-IR, V̇O2max) and muscle biochemical/molecular (vastus lateralis; mtDNAnum, mitochondrial and glycolytic enzymes activity, lipid content and markers of lipid peroxidation) measurements were performed in three groups of overweight, middle-aged male volunteers (n = 10 per group): sedentary T2DM (ST2DM); sedentary control (SC) and non-sedentary control (NSC), who differed in aerobic capacity (ST2DM < SC < NSC).

Results

mtDNAnum was greater in NSC versus SC and ST2DM (P < 0.001; P < 0.001), and less in ST2DM versus SC (P < 0.01). Across all groups, mtDNAnum positively correlated with ISI (P < 0.001; r = 0.688) and V̇O2max (normalised to free fat mass; r = 0.684, P < 0.001), and negatively correlated to HOMA-IR (r = −0.544, P < 0.01). The activity of mitochondrial enzymes (GluDH, CS and β-HAD) was greater in NSC than ST2DM (P < 0.01, P < 0.001 and P < 0.05) and SC (P < 0.05, P < 0.01 and P < 0.05), but similar between ST2DM and SC. Intramuscular-free fatty acids, triglycerides and malondialdehyde contents were similar between ST2DM and SC.

Conclusions

Body composition and indices of muscle mitochondrial volume/function were similar between SC and ST2DM. However, mtDNAnum differed and was positively associated with ISI, HOMA-IR and V̇O2max across all groups. Collectively, the findings support the contention that habitual physical activity is a key component of T2DM development, possibly by influencing mtDNAnum.

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Acknowledgements

This work was supported by the Medical Research Council [grant number MR/P021220/1]. The authors would like to thank the volunteers who participated in the present study.

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Authors and Affiliations

  1. MRC/ARUK Centre for Musculoskeletal Ageing Research, National Institute for Health Research Nottingham Biomedical Research Centre, School of Life Sciences, Nottingham University Medical School, Nottingham, NG7 2UH, UK

    Dumitru Constantin-Teodosiu, Despina Constantin & Paul L. Greenhaff

  2. NUTRIM School for Nutrition and Translational Research in Metabolism, Department of Human Biology and Movement Sciences, Maastricht University Medical Centre, Maastricht, The Netherlands

    Maurice M. Pelsers, Lex B. Verdijk & Luc van Loon

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  1. Dumitru Constantin-Teodosiu
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Contributions

DC-T—conducting experiments, collection, analysis, and interpretation of data, figures, literature search, writing of the manuscript and final approval. DC—data collection, analysis and interpretation, writing of the manuscript and final approval. MMP—study design, conducting experiments, and manuscript final approval. LBV—study design, conducting experiments and manuscript final approval. LvL—study design, data interpretation and manuscript final approval. PLG—data interpretation, writing of the manuscript and final approval.

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Correspondence to Dumitru Constantin-Teodosiu.

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Constantin-Teodosiu, D., Constantin, D., Pelsers, M.M. et al. Mitochondrial DNA copy number associates with insulin sensitivity and aerobic capacity, and differs between sedentary, overweight middle-aged males with and without type 2 diabetes. Int J Obes 44, 929–936 (2020). https://doi.org/10.1038/s41366-019-0473-2

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