Dataset Information

Endurance performance and energy metabolism during exercise in mice with a muscle-specific defect in the control of branched-chain amino acid catabolism.

ABSTRACT: It is known that the catabolism of branched-chain amino acids (BCAAs) in skeletal muscle is suppressed under normal and sedentary conditions but is promoted by exercise. BCAA catabolism in muscle tissues is regulated by the branched-chain ?-keto acid (BCKA) dehydrogenase complex, which is inactivated by phosphorylation by BCKA dehydrogenase kinase (BDK). In the present study, we used muscle-specific BDK deficient mice (BDK-mKO mice) to examine the effect of uncontrolled BCAA catabolism on endurance exercise performance and skeletal muscle energy metabolism. Untrained control and BDK-mKO mice showed the same performance; however, the endurance performance enhanced by 2 weeks of running training was somewhat, but significantly less in BDK-mKO mice than in control mice. Skeletal muscle of BDK-mKO mice had low levels of glycogen. Metabolome analysis showed that BCAA catabolism was greatly enhanced in the muscle of BDK-mKO mice and produced branched-chain acyl-carnitine, which induced perturbation of energy metabolism in the muscle. These results suggest that the tight regulation of BCAA catabolism in muscles is important for homeostasis of muscle energy metabolism and, at least in part, for adaptation to exercise training.

SUBMITTER: Xu M

PROVIDER: S-EPMC5515431 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Endurance performance and energy metabolism during exercise in mice with a muscle-specific defect in the control of branched-chain amino acid catabolism.

Xu Minjun M Kitaura Yasuyuki Y Ishikawa Takuya T Kadota Yoshihiro Y Terai Chihaya C Shindo Daichi D Morioka Takashi T Ota Miki M Morishita Yukako Y Ishihara Kengo K Shimomura Yoshiharu Y

PloS one 20170718 7

It is known that the catabolism of branched-chain amino acids (BCAAs) in skeletal muscle is suppressed under normal and sedentary conditions but is promoted by exercise. BCAA catabolism in muscle tissues is regulated by the branched-chain α-keto acid (BCKA) dehydrogenase complex, which is inactivated by phosphorylation by BCKA dehydrogenase kinase (BDK). In the present study, we used muscle-specific BDK deficient mice (BDK-mKO mice) to examine the effect of uncontrolled BCAA catabolism on endura ...[more]

PMID: 28719620

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Project description:Despite the role of branched-chain amino acids (BCAAs) in physiological processes such as nutrient signaling and protein synthesis, there is ongoing debate about the link between circulating BCAAs and insulin resistance (IR) in various populations. In healthy women, IR mildly increases during pregnancy, whereas both BCAAs and markers of BCAA catabolism decrease, indicating that fetal growth is being prioritized. Exercise reduces IR in nonpregnant adults, but less is known about the effect of exercise during pregnancy in women with obesity on IR and BCAA breakdown. The aim of this study was to determine the effect of a moderate-intensity exercise intervention during pregnancy on maternal circulating BCAAs and markers of BCAA catabolism [short-chain acylcarnitines (ACs)], and their associations with IR. Healthy obese [n = 80, means ± SD; body mass index (BMI): 36.9 ± 5.7 kg/m2] pregnant women were randomized into an exercise (n = 40, aerobic/resistance 3×/wk, ∼13th gestation week until birth) or a nonexercise control (n = 40) group. Blood was collected at 12.2 ± 0.5 and 36.0 ± 0.4 gestation weeks and analyzed for BCAA-derived acylcarnitine concentrations as markers of BCAA breakdown toward oxidative pathways, and glucose and insulin concentrations [updated homeostatic model assessment of IR (HOMA2-IR)]. After adjusting for HOMA2-IR, there were no interaction effects of group by time. In addition, there was a main positive effect of time on HOMA2-IR (12 wk: 2.3 ± 0.2, 36 wk: 3.0 ± 0.2, P = 0.003). A moderate-intensity exercise intervention during pregnancy in women with obesity was not associated with changes in BCAA-derived ACs versus standard of care. The decrease in BCAA-derived ACs throughout gestation could not be explained by IR.NEW & NOTEWORTHY This research showed an increase in insulin resistance (IR) and decrease in branched-chain amino acid catabolism throughout gestation in women with obesity, and addition of a moderate exercise intervention (known to attenuate IR in nonpregnant populations) did not alter these shifts. Findings provide support for metabolic safety of exercise during pregnancy.

Dataset Information

Endurance performance and energy metabolism during exercise in mice with a muscle-specific defect in the control of branched-chain amino acid catabolism.

Publications

Endurance performance and energy metabolism during exercise in mice with a muscle-specific defect in the control of branched-chain amino acid catabolism.

Similar Datasets

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