Involvement of ammonia metabolism in the improvement of endurance performance by tea catechins in mice

Shu Chen,Noriyasu Ota,Takahiro Hasumura,Akira Shimotoyodome,Yoshihiko Minegishi

doi:10.1038/s41598-020-63139-9

Abstract

Blood ammonia increases during exercise, and it has been suggested that this increase is both a central and peripheral fatigue factor. Although green tea catechins (GTCs) are known to improve exercise endurance by enhancing lipid metabolism in skeletal muscle, little is known about the relationship between ammonia metabolism and the endurance-improving effect of GTCs. Here, we examined how ammonia affects endurance capacity and how GTCs affect ammonia metabolism in vivo in mice and how GTCs affect mouse skeletal muscle and liver in vitro. In mice, blood ammonia concentration was significantly negatively correlated with exercise endurance capacity, and hyperammonaemia was found to decrease whole-body fat expenditure and fatty acid oxidation–related gene expression in skeletal muscle. Repeated ingestion of GTCs combined with regular exercise training improved endurance capacity and the expression of urea cycle–related genes in liver. In C2C12 myotubes, hyperammonaemia suppressed mitochondrial respiration; however, pre-incubation with GTCs rescued this suppression. Together, our results demonstrate that hyperammonaemia decreases both mitochondrial respiration in myotubes and whole-body aerobic metabolism. Thus, GTC-mediated increases in ammonia metabolism in liver and resistance to ammonia-induced suppression of mitochondrial respiration in skeletal muscle may underlie the endurance-improving effect of GTCs.

Highlights

Blood ammonia increases during exercise, and it has been suggested that this increase is both a central and peripheral fatigue factor
The rate of increase of blood ammonia concentration was significantly negatively correlated with total running time, which was measured as an index of exercise endurance capacity (Fig. 1B; r = −0.57, P < 0.05)
Ammonium chloride dose-dependently increased blood ammonia concentration, and the maximum blood ammonia concentration in the mice administered 100 mg/ kg-body weight (BW) ammonium chloride, which was reached at 10 min after administration, was comparable with that induced by exercise (Fig. 1A)

Summary

Introduction

Blood ammonia increases during exercise, and it has been suggested that this increase is both a central and peripheral fatigue factor. Blood ammonia concentration was significantly negatively correlated with exercise endurance capacity, and hyperammonaemia was found to decrease whole-body fat expenditure and fatty acid oxidation–related gene expression in skeletal muscle. Since plasma concentrations of ammonia during exercise often reach or exceed those found in liver disease patients[14,15], these toxic effects may be transiently induced during exercise, resulting in muscle fatigue It remains www.nature.com/scientificreports unknown whether these observed localised effects of hyperammonaemia disrupt energy metabolism throughout the whole body. Supplementation with amino acids that are components of the urea cycle, such as citrulline, arginine, and ornithine, has been reported to improve endurance by decreasing blood ammonia concentration during exercise[16,17]. Activation of the urea cycle may be one way of reducing fatigue and improving exercise endurance capacity

Methods

Results

Conclusion