Rose 2019 Am J Physiol Endocrinol Metab
|Rose S, Carvalho E, Diaz EC, Cotter M, Bennuri SC, Azhar G, Frye RE, Adams SH, Børsheim E (2019) A Comparative Study of Mitochondrial Respiration in Circulating Blood Cells and Skeletal Muscle Fibers in Women. Am J Physiol Endocrinol Metab [Epub ahead of print].|
Abstract: Skeletal muscle mitochondrial respiration is thought to be altered in obesity, insulin resistance and type 2 diabetes; however, the invasive nature of tissue biopsies is an important limiting factor for studying mitochondrial function. Recent findings suggest that bioenergetics profiling of circulating cells may inform on mitochondrial function in other tissues in lieu of biopsies. Thus, we sought to determine whether mitochondrial respiration in circulating cells (peripheral blood mononuclear cells [PBMCs] and platelets) reflects that of skeletal muscle fibers derived from the same subjects. PBMCs, platelets and skeletal muscle (vastus lateralis) samples were obtained from 32 young (25-35 years) women of varying BMIs. Using extracellular flux analysis and high-resolution respirometry, mitochondrial respiration was measured in intact blood cells as well as in permeabilized cells and permeabilized muscle fibers. Respiratory parameters were not correlated between permeabilized muscle fibers and intact PBMCs or platelets. In a sub-set of samples with permeabilized blood cells available, raw measures of substrate (pyruvate, malate, glutamate, and succinate)-driven respiration did not correlate between permeabilized muscle (per mg tissue) and permeabilized PBMCs (per 106 cells); however, complex I leak and OXPHOS coupling efficiency correlated between permeabilized platelets and muscle (Spearman's ρ = 0.64; p = 0.030, Spearman's ρ = 0.72; p = 0.010; respectively). Our data indicate that bioenergetics phenotypes in circulating cells cannot recapitulate muscle mitochondrial function. Select circulating cell bioenergetics phenotypes may possibly inform on overall metabolic health, but this postulate awaits validation in cohorts spanning a larger range of insulin resistance and type 2 diabetes status.
Labels: MiParea: Respiration, Comparative MiP;environmental MiP
Organism: Human Tissue;cell: Skeletal muscle, Blood cells, Platelet Preparation: Permeabilized cells, Permeabilized tissue, Intact cells
Coupling state: LEAK, OXPHOS, ET Pathway: F, N, S, NS, ROX HRR: Oxygraph-2k
Labels, 2019-07, PBMCs