https://www.biorxiv.org/content/10.1101/2024.08.19.608601v1.full
Resting studies showed decreased mitochondrial respiration including decreases in complex I (-36%) and II (-28%) as well as total electron system capacity (-34%) and electron system capacity coupled to ATP production via ATP synthase (-30%). Regarding muscle carbohydrate metabolism, SED individuals showed a decrease in mitochondrial pyruvate oxidation (-37%) as well as reduced expression (-49%) of mitochondrial pyruvate carrier (MPC). Regarding fatty acid metabolism, SED showed decreased activity of carnitine palmitoyltransferase I (CPT1)(-51%) and CPT2 (-44%) as well as decreased mitochondrial fatty acid oxidation (-35%). Metabolomics analysis also confirmed downregulation of carbohydrate and fat metabolism. Partial Least-Squares Discriminant Analysis (PLS-DA) identified distinct metabolic phenotypes through intermediates of glycolysis and fatty acid oxidation. Further, we found significant differences in cardiolipin (CL) species expression between SED and AC groups, which, due to the important role of CL in mitochondrial structure, function, biogenesis and bioenergetics, deserves further attention.
CONCLUSIONS
- – Sedentary individuals possess significant decreases in mitochondrial respiration as well as muscle bioenergetics during resting conditions compared to moderately active individuals.
– Despite similar GLUT-4 concentrations, sedentary individuals show significant decreased pyruvate oxidation as well as expression of mitochondrial pyruvate carrier (MPC).
– During exercise studies, sedentary individuals show significantly decreased levels of fat oxidation and lactate clearance capacity which correlate with mitochondrial and bioenergetics parameters from resting muscle biopsies. Hence, cardiopulmonary exercise testing (CPET) accompanied by measuring blood lactate levels could be a practical manner to assess muscle mitochondrial function and bioenergetics in a non-invasive and ambulatory manner.
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