Deficiency of electron transport chain in human skeletal muscle mitochondria in type 2 diabetes mellitus and obesity.
Level 4 - case-series / case-control
Cross-sectional comparative study relying partly on historical control data
PubMed 19887598 · doi:10.1152/ajpendo.00317.2009
What was done
The study assessed mitochondrial content and enzyme activities in frozen skeletal muscle biopsies from sedentary lean volunteers and compared them with historical data from obese individuals and individuals with type 2 diabetes mellitus (T2DM). The authors measured markers of mitochondrial mass (cardiolipin content and mtDNA), electron transport chain function (NADH oxidase activity), the tricarboxylic acid cycle (citrate synthase activity), and beta-oxidation (beta-hydroxyacyl-CoA dehydrogenase [beta-HAD] activity).
What was found
Total NADH oxidase activity was significantly reduced in the obese and T2DM cohorts compared to the lean cohort. Specific NADH oxidase activity per milligram of cardiolipin, as well as the NADH oxidase/citrate synthase and NADH oxidase/beta-HAD ratios, were reduced two- to threefold in both T2DM and obesity. Cardiolipin content, mtDNA content, and beta-HAD activity did not differ significantly between groups, though cardiolipin showed a non-significant tendency to decline in T2DM. Citrate synthase activity was significantly increased in the obese group compared to the lean group, but was similar between lean and T2DM subjects. Absolute numerical values, variances, and exact p-values were not provided in the abstract.
Why it matters
These findings suggest that mitochondrial oxidative deficits in skeletal muscle associated with obesity and type 2 diabetes stem from qualitative deficiencies in electron transport chain complexes rather than an overall reduction in mitochondrial content.
Limits
Sample sizes, participant demographics, and exact quantitative data with confidence intervals were omitted from the abstract. Comparing newly collected lean samples to frozen biopsies and historical data from previous studies introduces potential confounding and batch effects. In vitro enzyme assays in frozen tissue cannot fully capture in vivo mitochondrial respiration.
Cited by
- context Mitochondrial function in individuals with diabetes is approximately half that of the normal population.