The Impact of Cardiorespiratory Fitness on Cytotoxic T Cell Metabolism and Function
Justin C. Crane, Charles F. Hodgman, Rebekah M. Maddux, Heather L. Caslin, Mitzie Laughlin, Stacey L. Gorniak, Emily C. LaVoyPurpose:
Cardiorespiratory fitness (CRF) is associated with enhanced leukocyte metabolism. Whether CRF impacts the metabolism of specific leukocytes such as cytotoxic T cells (Tc) is unknown. As Tc metabolism and function, including interferon (IFN)-γ production, are linked, metabolic changes associated with higher CRF could impact Tc function. Therefore, this study aimed to determine whether CRF predicted Tc metabolism and function.
Methods:
Forty-three adults (16 women) underwent a maximal oxygen consumption (VO2peak) test, had body fat percentage (BF%) measured, and donated resting blood. Tc mitochondrial mass, mitochondrial membrane potential, fatty acid and amino acid oxidation (FAO and AAO) capacity, glycolytic capacity, and IFN-γ expression were assessed via flow cytometry. Linear regression assessed CRF and BF% as predictors of metabolism and function. Analyses were conducted within total Tc and in Tc subsets.
Results:
CRF predicted FAO and AAO capacity of Tc (ꞵ= 0.362; p= 0.017) and Tc subsets, and glycolytic capacity of Tc (ꞵ= 0.495; p< 0.001), central memory Tc (ꞵ= 0.304; p= 0.047), and effector memory re-expressing CD45RA (EMRA) Tc subsets (ꞵ= 0.451; p= 0.003). CRF also predicted IFN-γ expression by Tc (ꞵ= 0.384; p= 0.011), naïve Tc (ꞵ= 0.358; p= 0.020), and EMRA Tc subsets (ꞵ= 0.349; p= 0.022). Inclusion of BF% in models partially abrogated these relationships. CRF remained a significant predictor of Tc and EMRA Tc glycolytic capacity, and Tc function.
Conclusions:
CRF predicts Tc metabolism and function in healthy adults, where greater CRF associates with greater Tc FAO and AAO capacity, glycolytic capacity, and function. However, these relationships are in part attenuated by BF%, and Tc subsets exhibit differences in the degree to which they relate to CRF and BF%.