Metabolic flexibility

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Metabolic flexibility is the capacity to alter metabolism in response to exercise or available fuel (especially fats and carbohydrates). Metabolic inflexibility was first described as the ability to generate energy through either aerobic or anaerobic respiration[1] or as the inability of muscle to increase glucose oxidation in response to insulin.[2]

An organism can also be said to have metabolic flexibility if it is capable of metabolizing either carbohydrate or fat efficiently, depending on availability of those fuels.[3] By this definition, metabolic flexibility can be quantified using respiratory quotient.[4] This form of metabolic flexibility is reduced by insulin resistance.[5]

With aging there is a decrease in metabolic flexibility due to a decline in pyruvate dehydrogenase activity which results in pyruvate increasingly being anaerobically converted to lactate rather than aerobically converted to acetyl-CoA.[6] Similarly, a virus-induced cytokine storm can compromise metabolic flexibility by inactivating the pyruvate dehydrogenase complex and other enzymes.[7]

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References[edit]

  1. ^ Goodpaster BH, Sparks LM (2017). "Metabolic Flexibility in Health and Disease". Cell Metabolism. 25 (5): 1027–1036. doi:10.1016/j.cmet.2017.04.015. PMC 5513193. PMID 28467922.
  2. ^ Kelley DE, Mandarino LJ (2000). "Fuel selection in human skeletal muscle in insulin resistance: a reexamination". Diabetes. 49 (2): 677–683. doi:10.2337/diabetes.49.5.677. PMID 10905472.
  3. ^ Park S, Jeon JH, Lee IK (2018). "Role of the Pyruvate Dehydrogenase Complex in Metabolic Remodeling: Differential Pyruvate Dehydrogenase Complex Functions in Metabolism". Diabetes Medical Journal. 42 (4): 270–281. doi:10.4093/dmj.2018.0101. PMC 6107359. PMID 30136450.
  4. ^ Thyfault JP, Morris EM (2017). "Intrinsic (Genetic) Aerobic Fitness Impacts Susceptibility for Metabolic Disease". Exercise and Sport Sciences Reviews. 45 (1): 7–15. doi:10.1249/JES.0000000000000087. PMC 5161693. PMID 27433978.
  5. ^ Cao X, Thyfault JP (2023). "Exercise drives metabolic integration between muscle, adipose and liver metabolism and protects against aging-related diseases". Experimental Gerontology. 176: 112178. doi:10.1016/j.exger.2023.112178. PMID 37085127.
  6. ^ Veech RL, Bradshaw PC, King MT (2017). "Ketone bodies mimic the life span extending properties of caloric restriction". IUBMB Life. 69 (5): 305–314. doi:10.1002/iub.1627. PMID 28371201.
  7. ^ Bradshaw PC, Seeds WA, Curtis WM (2020). "COVID-19: Proposing a Ketone-Based Metabolic Therapy as a Treatment to Blunt the Cytokine Storm". Oxidative Medicine and Cellular Longevity. 2020: 6401341. doi:10.1155/2020/6401341. PMC 7519203. PMID 33014275.