TY - JOUR
T1 - Blunted fat oxidation upon submaximal exercise is partially compensated by enhanced glucose metabolism in children, adolescents, and young adults with Barth syndrome
AU - Cade, William Todd
AU - Bohnert, Kathryn L.
AU - Peterson, Linda R.
AU - Patterson, Bruce W.
AU - Bittel, Adam J.
AU - Okunade, Adewole L.
AU - de las Fuentes, Lisa
AU - Steger-May, Karen
AU - Bashir, Adil
AU - Schweitzer, George G.
AU - Chacko, Shaji K.
AU - Wanders, Ronald J.
AU - Pacak, Christina A.
AU - Byrne, Barry J.
AU - Reeds, Dominic N.
PY - 2019/5
Y1 - 2019/5
N2 - 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.
AB - 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.
KW - Barth syndrome
KW - exercise
KW - fatty acid
KW - mitochondria
UR - http://www.scopus.com/inward/record.url?scp=85064815330&partnerID=8YFLogxK
U2 - 10.1002/jimd.12094
DO - 10.1002/jimd.12094
M3 - Article
C2 - 30924938
AN - SCOPUS:85064815330
VL - 42
SP - 480
EP - 493
JO - Journal of Inherited Metabolic Disease
JF - Journal of Inherited Metabolic Disease
SN - 0141-8955
IS - 3
ER -