Abstract
Metabolic and bioenergetic dysfunction are associated with oxidative stress and thought to be a common underlying mechanism of chronic diseases such as atherosclerosis, diabetes, and neurodegeneration. Recent findings support an emerging concept that circulating leukocytes and platelets can act as sensors or biomarkers of mitochondrial function in patients subjected to metabolic diseases. It is proposed that systemic stress-induced alterations in leukocyte bioenergetics are the consequence of several factors including reactive oxygen species. This suggests that oxidative stress mediated changes in leukocyte mitochondrial function could be used as an indicator of bioenergetic health in individuals. To test this concept, we investigated the effect of the redox cycling agent, 2,3 dimethoxynaphthoquinone (DMNQ) on the bioenergetic profiles of monocytes isolated from healthy human subjects using the extracellular flux analyzer. In addition, we tested the hypothesis that the bioenergetic health index (BHI), a single value that represents the bioenergetic health of individuals, is dynamically sensitive to oxidative stress in human monocytes. DMNQ decreased monocyte ATP-linked respiration, maximal respiration, and reserve capacity and caused an increase in proton leak and non-mitochondrial respiration compared to monocytes not treated with DMNQ. The BHI was a more sensitive indicator of the DMNQ-dependent changes in bioenergetics than any individual parameter. These data suggest that monocytes are susceptible to oxidative stress mediated by DMNQ and this can be accurately assessed by the BHI. Taken together, our findings suggest that the BHI has the potential to act as a functional biomarker of the impact of systemic oxidative stress in patients with metabolic disorders.