Chronic exercise improves hepatic acylcarnitine handling

• Published in: iScience 2024-03, Vol.27 (3), p.109083-109083, Article 109083
• Main Authors: Hernández-Saavedra, Diego, Hinkley, J. Matthew, Baer, Lisa A., Pinckard, Kelsey M., Vidal, Pablo, Nirengi, Shinsuke, Brennan, Andrea M., Chen, Emily Y., Narain, Niven R., Bussberg, Valerie, Tolstikov, Vladimir V., Kiebish, Michael A., Markunas, Christina, Ilkayeva, Olga, Goodpaster, Bret H., Newgard, Christopher B., Goodyear, Laurie J., Coen, Paul M., Stanford, Kristin I.
• Format: Article
• Language: English
• Subjects: Cell biology; Health sciences; Physiology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2024.109083

Exercise mediates tissue metabolic function through direct and indirect adaptations to acylcarnitine (AC) metabolism, but the exact mechanisms are unclear. We found that circulating medium-chain acylcarnitines (AC) (C12-C16) are lower in active/endurance trained human subjects compared to sedentary controls, and this is correlated with elevated cardiorespiratory fitness and reduced adiposity. In mice, exercise reduced serum AC and increased liver AC, and this was accompanied by a marked increase in expression of genes involved in hepatic AC metabolism and mitochondrial β-oxidation. Primary hepatocytes from high-fat fed, exercise trained mice had increased basal respiration compared to hepatocytes from high-fat fed sedentary mice, which may be attributed to increased Ca2+ cycling and lipid uptake into mitochondria. The addition of specific medium- and long-chain AC to sedentary hepatocytes increased mitochondrial respiration, mirroring the exercise phenotype. These data indicate that AC redistribution is an exercise-induced mechanism to improve hepatic function and metabolism. [Display omitted] •Chronic exercise training reduces serum acylcarnitines (AC) in mice and humans•Hepatic AC facilitates mitochondrial respiration•Exercise enhances liver AC metabolism by increasing fatty acid uptake and Ca2+ cycling Health sciences; Physiology; Cell biology