Effects of eccentric exercise on branched‐chain amino acid profiles in rat serum and skeletal muscle

Qun, Zuo; Xinkai, Y.; Wang, Jing

doi:10.1111/jpn.12062

Cited by 7 publications

(3 citation statements)

References 42 publications

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“…The comprehensive serum metabolite signatures induced by acute resistance exercise include decreased amino acids and increased fatty acids. These findings are consistent with previous observations that the oxidation and catabolism of amino acids, especially branched-chain amino acids (BCAA), are promoted by exercise (Qun et al, 2014), while the mobilization of free fatty acids from depots and efflux of plasma free fatty acids are increased by exercise (Friedberg et al, 1963;Shimomura et al, 2004). Importantly, the metabolites of valine, i.e., alpha-ketoisovaleric acid (akeval) and 2-hydroxy-3-methylbutyric acid (2H3MA), as well as a metabolite of alanine, pyruvic acid (Pyr), were also increased after acute exercise.…”

Section: Discussionsupporting

confidence: 93%

Exercise‐induced α‐ketoglutaric acid stimulates muscle hypertrophy and fat loss through OXGR1‐dependent adrenal activation

Yuan¹,

Jiang³

et al. 2020

The EMBO Journal

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Beneficial effects of resistance exercise on metabolic health and particularly muscle hypertrophy and fat loss are well established, but the underlying chemical and physiological mechanisms are not fully understood. Here, we identified a myometabolite‐mediated metabolic pathway that is essential for the beneficial metabolic effects of resistance exercise in mice. We showed that substantial accumulation of the tricarboxylic acid cycle intermediate α‐ketoglutaric acid (AKG) is a metabolic signature of resistance exercise performance. Interestingly, human plasma AKG level is also negatively correlated with BMI. Pharmacological elevation of circulating AKG induces muscle hypertrophy, brown adipose tissue (BAT) thermogenesis, and white adipose tissue (WAT) lipolysis in vivo. We further found that AKG stimulates the adrenal release of adrenaline through 2‐oxoglutarate receptor 1 (OXGR1) expressed in adrenal glands. Finally, by using both loss‐of‐function and gain‐of‐function mouse models, we showed that OXGR1 is essential for AKG‐mediated exercise‐induced beneficial metabolic effects. These findings reveal an unappreciated mechanism for the salutary effects of resistance exercise, using AKG as a systemically derived molecule for adrenal stimulation of muscle hypertrophy and fat loss.

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Section: Discussionsupporting

confidence: 93%

Exercise‐induced α‐ketoglutaric acid stimulates muscle hypertrophy and fat loss through OXGR1‐dependent adrenal activation

Yuan¹,

Jiang³

et al. 2020

The EMBO Journal

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show abstract

“…The comprehensive serum metabolite signatures induced by acute resistance exercise include decreased amino acids and increased fatty acids. These findings are consistent with previous observations that the oxidation and catabolism of amino acids, especially branched-chain amino acids (BCAA), are promoted by exercise (Qun et al, 2014), while the mobilization of free fatty acids from depots and efflux of plasma free fatty acids are increased by exercise (Friedberg et al, 1963; Shimomura et al, 2004). Importantly, the metabolites of valine, i.e., alpha-ketoisovaleric acid (α-keval) and 2-hydroxy-3-methylbutyric acid (2H3MA), as well as a metabolite of alanine, pyruvic acid (Pyr), were also increased after acute exercise.…”

Section: Discussionsupporting

confidence: 92%

α-ketoglutaric acid stimulates muscle hypertrophy and fat loss through OXGR1-dependent adrenal activation

Yuan

Jiang

et al. 2019

Preprint

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Running title: α-ketoglutaric acid stimulates lipolysis through OXGR1 31 32 Conflict of interest statement 33The authors have declared that no conflict of interest exists. 34 35 36 37 38 39 40 41 42 43 44 3 Summary: Beneficial effects of resistance exercise on metabolic health and particularly muscle 45hypertrophy and fat loss are well established, but the underlying chemical and physiological 46 mechanisms are not fully understood. Here we identified a myometabolite-mediated metabolic 47 pathway that is essential for the beneficial metabolic effects of resistance exercise in vivo. We showed 48 that substantial accumulation of the tricarboxylic acid cycle intermediate α-ketoglutaric acid (AKG) is 49 a metabolic signature of resistance exercise performance. Interestingly, human plasma AKG level is 50 also negatively correlated with BMI. Pharmacological elevation of circulating AKG induces muscle 51 hypertrophy, brown adipose tissue (BAT) thermogenesis, and white adipose tissue (WAT) lipolysis in 52 vivo. We further found that AKG stimulates the adrenal release of adrenaline through 2-oxoglutarate 53 receptor 1 (OXGR1) expressed in adrenal glands. Finally, by using both loss-of-function and 54 gain-of-function mouse models, we showed that OXGR1 is essential for AKG-mediated 55 exercise-induced beneficial metabolic effects. These findings reveal an unappreciated mechanism for 56 the salutary effects of resistance exercise, using AKG as a systemically-derived molecule for adrenal 57 stimulation of muscle hypertrophy and fat loss. 58 59 Keywords: AKG/lipolysis /obesity/OXGR1/thermogenesis. 60 61 62 63 64 5 provide signatures of endurance exercise performance and cardiovascular disease susceptibility, and 88also identify molecular pathways that may modulate the salutary effects on cardiovascular function. 89However, very few metabolomics data is available for resistance exercise (Berton et al, 2017; Li et al, 90 2012), and the underlying chemical and physiological mechanisms for the stimulatory effects of 91 resistance exercise on fat loss and muscle hypertrophy are not fully understood. Our goal is to identify 92 the essential mediator for the beneficial metabolic effects of resistance exercise and provide potential 93 therapeutic strategies to mimic the health effects of resistance exercise to combat obesity. 94 95Emerging evidence has identified skeletal muscle as secretory organs in regulating energy 96 homeostasis and obesity progression in other tissues (Ibrahim et al, 2017; Rai & Demontis, 2016). 97Exercise can induce systemic metabolic effects either via changes in the mass and metabolic demand 98 of muscle or via the release of muscle-derived cytokines (myokines) and metabolites (myometabolites) 99

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“…Three BCAA (valine, leucine, and isoleucine) were increased by both GW501516 and training. Long-distance running involves mobilization of BCAA 29 and many studies demonstrate that BCAA concentrations immediately after exercise are reduced in the serum, but not in muscle 30 . We found that training or GW501516 treatment, preserved serum BCAA levels after exhaustive running.…”

Section: Discussionmentioning

confidence: 99%

A metabolomic study of the PPARδ agonist GW501516 for enhancing running endurance in Kunming mice

Chen¹,

Gao

Xie³

et al. 2015

Sci Rep

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Exercise can increase peroxisome proliferator-activated receptor-δ (PPARδ) expression in skeletal muscle. PPARδ regulates muscle metabolism and reprograms muscle fibre types to enhance running endurance. This study utilized metabolomic profiling to examine the effects of GW501516, a PPARδ agonist, on running endurance in mice. While training alone increased the exhaustive running performance, GW501516 treatment enhanced running endurance and the proportion of succinate dehydrogenase (SDH)-positive muscle fibres in both trained and untrained mice. Furthermore, increased levels of intermediate metabolites and key enzymes in fatty acid oxidation pathways were observed following training and/or treatment. Training alone increased serum inositol, glucogenic amino acids, and branch chain amino acids. However, GW501516 increased serum galactose and β-hydroxybutyrate, independent of training. Additionally, GW501516 alone raised serum unsaturated fatty acid levels, especially polyunsaturated fatty acids, but levels increased even more when combined with training. These findings suggest that mechanisms behind enhanced running capacity are not identical for GW501516 and training. Training increases energy availability by promoting catabolism of proteins, and gluconeogenesis, whereas GW501516 enhances specific consumption of fatty acids and reducing glucose utilization.

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Effects of eccentric exercise on branched‐chain amino acid profiles in rat serum and skeletal muscle

Cited by 7 publications

References 42 publications

Exercise‐induced α‐ketoglutaric acid stimulates muscle hypertrophy and fat loss through OXGR1‐dependent adrenal activation

Exercise‐induced α‐ketoglutaric acid stimulates muscle hypertrophy and fat loss through OXGR1‐dependent adrenal activation

α-ketoglutaric acid stimulates muscle hypertrophy and fat loss through OXGR1-dependent adrenal activation

A metabolomic study of the PPARδ agonist GW501516 for enhancing running endurance in Kunming mice

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