Blood-based bioenergetic profiling is related to differences in brain morphology in African Americans with Type 2 diabetes

Abstract

Blood-based bioenergetic profiling has promising applications as a minimally invasive biomarker of systemic bioenergetic capacity. In the present study, we examined peripheral blood mononuclear cell (PBMC) mitochondrial function and brain morphology in a cohort of African Americans with long-standing Type 2 diabetes. Key parameters of PBMC respiration were correlated with white matter, gray matter, and total intracranial volumes. Our analyses indicate that these relationships are primarily driven by the relationship of systemic bioenergetic capacity with total intracranial volume, suggesting that systemic differences in mitochondrial function may play a role in overall brain morphology.

Keywords: bioenergetics; diabetes; mitochondria; neuroimaging.

Figure 1:

Representative graphs of the two different techniques used to measure PBMC respirometry. Bioenergetic profiles of PBMCs isolated from one participant. Respiration is measured as oxygen consumption rate. Figure1A: Representative graph generated by the Seahorse XF24–3 extracellular flux analyzer. Figure1B: Representative graph generated by the Oroboros O2K respirometer. As shown in Figure 1A, injections were as follows: O=oligomycin, U=uncoupler (FCCP), R=rotenone, A=antimycin A. As shown in Figure 1B, multiple substrates and inhibitors were sequentially added to permeabilized cells and measure oxygen flux due to fatty acid oxidation, followed by oxidative phosphorylation. D=adenosine diphosphate, Dig=Digitonin, Oct=Octanoylcarnitine, M1=0.1M malate, M2=0.8M malate, c=cytochrome c, P=pyruvate, G=glutamate, S=succinate, Gp=glycerophosphate, U=uncoupler (FCCP), R=rotenone, A=antimycin A.