Disruption of hepatic mitochondrial pyruvate and amino acid metabolism impairs gluconeogenesis and endurance exercise capacity in mice

Author:

Martino Michael R.1,Habibi Mohammad1,Ferguson Daniel1,Brookheart Rita T.1,Thyfault John P.2ORCID,Meyer Gretchen A.3ORCID,Lantier Louise4ORCID,Hughey Curtis C.5ORCID,Finck Brian N.1ORCID

Affiliation:

1. Division of Nutritional Sciences and Obesity Medicine, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States

2. Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, Missouri, United States

3. Department of Medicine, Program in Physical Therapy, Washington University School of Medicine, St. Louis, Missouri, United States

4. Department of Molecular Physiology and Biophysics, Vanderbilt Mouse Metabolic Phenotyping Center, Vanderbilt University School of Medicine, Nashville, Tennessee, United States

5. Division of Molecular Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, United States

Abstract

Martino and colleagues examined the effects of inhibiting hepatic gluconeogenesis on exercise performance and systemic metabolism during treadmill exercise in mice. Combined inhibition of gluconeogenesis from lactate/pyruvate and alanine impaired exercise endurance and led to hypoglycemia during and after exercise. In contrast, suppressing either pyruvate-mediated or alanine-mediated gluconeogenesis alone had no effect on these parameters. These findings provide new insight into the molecular nodes that coordinate the metabolic responses of muscle and liver during exercise.

Funder

HHS | NIH | National Heart, Lung, and Blood Institute

HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases

HHS | NIH | National Institute on Aging

U.S. Department of Veterans Affairs

Publisher

American Physiological Society

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