Because of their branched structure, the essential amino acids valine, leucine, and isoleucine are collectively referred to as the branched-chain amino acids (BCAAs). These amino acids play crucial roles in skeletal muscle , not only as a major component of proteins, but also as an energy source, especially during exercise [1, 2]. BCAAs are also involved in the regulation of protein metabolism in skeletal muscle cells; for example, leucine activates mammalian target of rapamycin complex 1 (mTORC1), which stimulates protein synthesis and suppresses proteolysis by autophagy . This activation of mTORC1 requires a high concentration of circulating leucine to be maintained .
Sarcopenia (i.e., a decrease in skeletal muscle mass) is a serious clinical problem associated with poorer prognosis in various diseases [5, 6]. Studies have reported a relationship between skeletal muscle mass and the concentration of circulating BCAAs in several diseases [7, 8]. Patients with chronic heart failure showed lower serum BCAA concentrations and Fisher's ratios than controls, with positive correlations between the values of their skeletal muscle index (SMI), defined as skeletal muscle mass divided by the squared height, and their BCAA concentrations and Fisher's ratios . In patients with chronic liver diseases, it was observed that lower BCAA to tyrosine ratios (BTRs) were associated with decreased skeletal muscle mass .
Through training, sports athletes increase their skeletal muscle mass for more effective energy use and improved competitive performance. Exercise induces an increase in whole-body energy expenditure and a prompt decrease in circulating BCAAs . Several studies have reported that BCAA supplementation reduces muscle damage and protein breakdown during exercise [10–12]. In circulating lipid metabolism, lipoprotein lipase (LPL) plays a crucial role in triglyceride (TG)-rich lipoprotein hydrolysis . LPL is highly expressed and synthesized in skeletal muscle tissues to use fatty acids for energy and translocated to the capillary lumen by glycosylphosphatidylinositol anchored high-density lipoprotein binding protein 1 (GPIHBP1), which has a vital role in LPL lipolytic processing . We previously reported that wrestling athletes with high levels of skeletal muscle had high concentrations of LPL and GPIHBP1, and that increasing skeletal muscle mass improved effective energy use by promoting the hydrolysis of TG-rich lipoproteins . However, the relationship between skeletal muscle mass and protein metabolism, including circulating BCAAs, has not been fully understood.
Thyroid hormones also play a vital role in energy metabolism in skeletal muscle . They increase oxygen consumption and resting metabolic rate through increased mitochondrial activity related to the stimulation of mitochondrial enzymes and uncoupling protein 3 . Thyroid hormones also promote skeletal muscle differentiation and induce the transition from slow to fast fibers by suppressing of Myh7 gene expression and through the stimulation of Myh1, Myh2, and Myh4 expression . However, the role of thyroid hormones in amino acid metabolism in skeletal muscle, especially that of BCAAs, has not been elucidated, and the relationships between serum concentrations of free thyroid hormones and BCAAs in athletes with regular high energy consumption are not known.
Nutritional indicators, such as levels of albumin and rapid turnover proteins, are often used as blood biomarkers for assessing the condition of athletes to help their good performance. However, few markers reflect the hypermetabolic state of athletes. If the relationship between skeletal muscle mass and the concentration of circulating BCAAs can be clarified in athletes, it may be possible to use BCAA concentration as a biomarker of the hypermetabolic state. In addition, clarification of the relationship between concentrations of circulating BCAAs and thyroid function tests could help elucidation of the novel mechanisms of BCAA metabolism via thyroid hormones in skeletal muscle. Concentrations of circulating BCAAs are typically detected by amino acid analysis using liquid chromatography–mass spectrometry, which is cumbersome and not widely available . In contrast, serum BTR, which provides a simple indication of circulating BCAA concentration and Fisher's ratio, can be measured conveniently.
The aim of this study was to investigate the associations between serum BTR, skeletal muscle mass, and thyroid function in young Japanese men, including athletes with high skeletal muscle mass, and to compare BTR to other nutritional indicators.