Dorothy M. Davis Heart and Lung Research Institute; Department of Physiology and Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH, USA; Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
J. Matthew Hinkley
AdventHealth Translational Research Institute, AdventHealth, Orlando, FL 32804, USA
Lisa A. Baer
Dorothy M. Davis Heart and Lung Research Institute; Department of Physiology and Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH, USA; Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
Kelsey M. Pinckard
Dorothy M. Davis Heart and Lung Research Institute; Department of Physiology and Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
Pablo Vidal
Dorothy M. Davis Heart and Lung Research Institute; Department of Physiology and Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH, USA; Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
Shinsuke Nirengi
Dorothy M. Davis Heart and Lung Research Institute; Department of Physiology and Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH, USA; Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
Andrea M. Brennan
AdventHealth Translational Research Institute, AdventHealth, Orlando, FL 32804, USA
Emily Y. Chen
BERG, Framingham, MA 01701, USA
Niven R. Narain
BERG, Framingham, MA 01701, USA
Valerie Bussberg
BERG, Framingham, MA 01701, USA
Vladimir V. Tolstikov
BERG, Framingham, MA 01701, USA
Michael A. Kiebish
BERG, Framingham, MA 01701, USA
Christina Markunas
Sarah W. Stedman Nutrition and Metabolism Center and Duke Molecular Physiology Institute, Departments of Pharmacology and Cancer Biology and Medicine, Durham, NC 27701, USA
Olga Ilkayeva
Sarah W. Stedman Nutrition and Metabolism Center and Duke Molecular Physiology Institute, Departments of Pharmacology and Cancer Biology and Medicine, Durham, NC 27701, USA
Bret H. Goodpaster
AdventHealth Translational Research Institute, AdventHealth, Orlando, FL 32804, USA
Christopher B. Newgard
Sarah W. Stedman Nutrition and Metabolism Center and Duke Molecular Physiology Institute, Departments of Pharmacology and Cancer Biology and Medicine, Durham, NC 27701, USA
Laurie J. Goodyear
Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Boston, MA 02215, USA
Paul M. Coen
AdventHealth Translational Research Institute, AdventHealth, Orlando, FL 32804, USA; Corresponding author
Kristin I. Stanford
Dorothy M. Davis Heart and Lung Research Institute; Department of Physiology and Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH, USA; Corresponding author
Summary: 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.
