Blunted fat oxidation upon submaximal exercise is partially compensated by enhanced glucose metabolism in children, adolescents, and young adults with Barth syndrome

William Todd Cade, Kathryn L. Bohnert, Linda R. Peterson, Bruce W. Patterson, Adam J. Bittel, Adewole L. Okunade, Lisa de las Fuentes, Karen Steger-May, Adil Bashir, George G. Schweitzer, Shaji K. Chacko, Ronald J. Wanders, Christina A. Pacak, Barry J. Byrne, Dominic N. Reeds

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Barth syndrome (BTHS) is a rare X-linked condition resulting in abnormal mitochondria, cardioskeletal myopathy, and growth delay; however, the effects of BTHS on substrate metabolism regulation and their relationships with tissue function in humans are unknown. We sought to characterize glucose and fat metabolism during rest, submaximal exercise, and postexercise rest in children, adolescents, and young adults with BTHS and unaffected controls and examine their relationships with cardioskeletal energetics and function. Children/adolescents and young adults with BTHS (n = 29) and children/adolescent and young adult control participants (n = 28, total n = 57) underwent an infusion of 6′6′H2 glucose and U-13C palmitate and indirect calorimetry during rest, 30-minutes of moderate exercise (50% (Formula presented.)), and recovery. Cardiac function, cardioskeletal mitochondrial energetics, and exercise capacity were examined via echocardiography, 31P magnetic resonance spectroscopy, and peak exercise testing, respectively. The glucose turnover rate was significantly higher in individuals with BTHS during rest (33.2 ± 9.8 vs 27.2 ± 8.1 μmol/kgFFM/min, P <.01) and exercise (34.7 ± 11.2 vs 29.5 ± 8.8 μmol/kgFFM/min, P <.05) and tended to be higher postexercise (33.7 ± 10.2 vs 28.8 ± 8.0 μmol/kgFFM/min, P <.06) compared to controls. Increases in total fat (−3.9 ± 7.5 vs 10.5 ± 8.4 μmol/kgFFM/min, P <.0001) and plasma fatty acid oxidation rates (0.0 ± 1.8 vs 5.1 ± 3.9 μmol/kgFFM/min, P <.0001) from rest to exercise were severely blunted in BTHS compared to controls. Conclusion: An inability to upregulate fat metabolism during moderate intensity exercise appears to be partially compensated by elevations in glucose metabolism. Derangements in fat and glucose metabolism are characteristic of the pathophysiology of BTHS. A severely blunted ability to upregulate fat metabolism during a modest level of physical activity is a defining pathophysiologic characteristic in children, adolescents, and young adults with BTHS.

Original languageEnglish
Pages (from-to)480-493
Number of pages14
JournalJournal of Inherited Metabolic Disease
Volume42
Issue number3
DOIs
StatePublished - May 2019

Keywords

  • Barth syndrome
  • exercise
  • fatty acid
  • mitochondria

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