Kinesiology and Applied Physiology
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Item Elevated LDL-C induces T-cell metabolic dysfunction and increases inflammation and oxidative stress in mid-life adults(Journal of Applied Physiology, 2025-08-04) DeConne, Theodore M.; Ghosh, Arit; Awad, Catherine; Fancher, Ibra S.; Edwards, David G.; Trott, Daniel W.; Martens, Christopher R.T-cells may contribute to chronic, low-grade, sustained inflammation and oxidative stress commonly observed with aging and chronic disease. T-cell metabolic alterations impact T-cell differentiation, inflammation, and oxidative stress in animal models. Low-density lipoprotein cholesterol (LDL-C) has been identified as a novel antigen that activates T-cells via a canonical pathway. However, in humans, little is known about the direct effect of LDL-C on T-cells. Endogenous LDL-C concentration peaks during mid-life in humans and may contribute to midlife chronic disease risk by inducing T-cell dysfunction. Thus, this study investigated the effects of exogenous LDL-C exposure on CD4+ and CD8+ T-cells from mid-life adults. Compared to a physiologically “low” LDL-C concentration, we hypothesized that exposure to “borderline high” LDL-C would induce activation, alter metabolism, and increase mitochondrial and inflammation and mitochondrial reactive oxygen species production in T-cells from mid-life adults. T-cell metabolism was assessed using extracellular flux analysis and all other outcomes were assessed using flow cytometry. Our findings indicate that exposure to a borderline high concentration of LDL-C induced CD4+ and CD8+ T-cell activation, impaired mitochondrial respiration, and increased glycolytic metabolism. Further, we observed exogenous LDL-C exposure induced T-cell differentiation towards activated effector memory and effector memory re-expressing CD45RA subpopulations and increased inflammatory cytokine and mitochondrial reactive oxygen species production. These data suggest that borderline high LDL-C induces T-cell dysfunction that may increase the risk for age-related diseases. Future observational and clinical research should investigate the effects of endogenous LDL-C and other blood lipids on in vivo T-cell function and the implications for disease risk.Item Clinical Exercise Physiology (MS) Program Policy Statement(2021-06) Department of Kinesiology and Applied PhysiologyItem Exercise Science (MS) Program Policy Statement(2021) Department of Kinesiology and Applied PhysiologyItem Athletic Training (MS) Program Policy Statement(2021-06) Department of Kinesiology and Applied PhysiologyItem Athletic Training (MS) Program Policy Statement(2020-06) Department of Kinesiology and Applied PhysiologyItem Clinical Exercise Physiology (MS) Program Policy Statement(2017-10-24) Department of Kinesiology and Applied PhysiologyItem Exercise Science (MS) Program Policy Statement(2017-11-01) Department of Kinesiology and Applied PhysiologyItem Applied Physiology (PhD) Program Policy Statement(2019-11) Department of Kinesiology and Applied Physiology
