PMID- 31641211
OWN - NLM
STAT- MEDLINE
DCOM- 20210802
LR  - 20220323
IS  - 1476-5497 (Electronic)
IS  - 0307-0565 (Linking)
VI  - 44
IP  - 4
DP  - 2020 Apr
TI  - 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.
PG  - 929-936
LID - 10.1038/s41366-019-0473-2 [doi]
AB  - BACKGROUND/OBJECTIVES: Increased risk of type 2 diabetes mellitus (T2DM) is 
      linked to impaired muscle mitochondrial function and reduced mitochondrial DNA 
      copy number (mtDNA(num)). 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, V̇O(2max)) was associated with skeletal muscle 
      mitochondrial volume and mtDNA(num), and was predictive of T2DM in overweight, 
      middle-aged men. METHODS: Whole-body physiological (ISI-insulin sensitivity 
      index, HOMA-IR, V̇O(2max)) and muscle biochemical/molecular (vastus lateralis; 
      mtDNA(num), 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: mtDNA(num) 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, mtDNA(num) positively correlated with ISI 
      (P < 0.001; r = 0.688) and V̇O(2max) (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 beta-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, mtDNA(num) differed and was 
      positively associated with ISI, HOMA-IR and V̇O(2max) across all groups. 
      Collectively, the findings support the contention that habitual physical activity 
      is a key component of T2DM development, possibly by influencing mtDNA(num).
FAU - Constantin-Teodosiu, Dumitru
AU  - Constantin-Teodosiu D
AUID- ORCID: 0000-0002-8448-5564
AD  - 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. 
      tim.constantin@nottingham.ac.uk.
FAU - Constantin, Despina
AU  - Constantin D
AD  - 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.
FAU - Pelsers, Maurice M
AU  - Pelsers MM
AD  - NUTRIM School for Nutrition and Translational Research in Metabolism, Department 
      of Human Biology and Movement Sciences, Maastricht University Medical Centre, 
      Maastricht, The Netherlands.
FAU - Verdijk, Lex B
AU  - Verdijk LB
AD  - NUTRIM School for Nutrition and Translational Research in Metabolism, Department 
      of Human Biology and Movement Sciences, Maastricht University Medical Centre, 
      Maastricht, The Netherlands.
FAU - van Loon, Luc
AU  - van Loon L
AUID- ORCID: 0000-0003-4435-0101
AD  - NUTRIM School for Nutrition and Translational Research in Metabolism, Department 
      of Human Biology and Movement Sciences, Maastricht University Medical Centre, 
      Maastricht, The Netherlands.
FAU - Greenhaff, Paul L
AU  - Greenhaff PL
AD  - 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.
LA  - eng
GR  - MR/K00414X/1/MRC_/Medical Research Council/United Kingdom
GR  - MR/P021220/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191022
PL  - England
TA  - Int J Obes (Lond)
JT  - International journal of obesity (2005)
JID - 101256108
RN  - 0 (DNA, Mitochondrial)
SB  - IM
MH  - DNA Copy Number Variations/genetics
MH  - DNA, Mitochondrial/*genetics
MH  - *Diabetes Mellitus, Type 2/complications/genetics
MH  - Exercise Tolerance/*genetics
MH  - Humans
MH  - Insulin Resistance/*genetics
MH  - Male
MH  - Middle Aged
MH  - *Overweight/complications/genetics
EDAT- 2019/10/24 06:00
MHDA- 2021/08/03 06:00
CRDT- 2019/10/24 06:00
PHST- 2019/04/12 00:00 [received]
PHST- 2019/09/30 00:00 [accepted]
PHST- 2019/09/19 00:00 [revised]
PHST- 2019/10/24 06:00 [pubmed]
PHST- 2021/08/03 06:00 [medline]
PHST- 2019/10/24 06:00 [entrez]
AID - 10.1038/s41366-019-0473-2 [pii]
AID - 10.1038/s41366-019-0473-2 [doi]
PST - ppublish
SO  - Int J Obes (Lond). 2020 Apr;44(4):929-936. doi: 10.1038/s41366-019-0473-2. Epub 
      2019 Oct 22.