Acute Aerobic Exercise Leads to Increased Plasma Levels of R- and S-β-Aminoisobutyric Acid in Humans.

Jan Stautemas,Inge Everaert,Fred Vaz,Wim Derave,Filip B D Lefevere,Laura Blancquaert,André B P Van Kuilenburg,Lida Stroomer

doi:10.3389/fphys.2019.01240

Abstract

Recently, it was suggested that β-aminoisobutyric acid (BAIBA) is a myokine involved in browning of fat. However, there is no evidence for an acute effect of exercise supporting this statement and the metabolic distinct enantiomers of BAIBA were not taken into account. Concerning these enantiomers, there is at this point no consensus about resting concentrations of plasma R- and S-BAIBA. Additionally, a polymorphism of the alanine - glyoxylate aminotransferase 2 (AGXT2) gene (rs37369) is known to have a high impact on baseline levels of total BAIBA, but the effect on the enantiomers is unknown. Fifteen healthy recreationally active subjects, with different genotypes of rs37369, participated in a randomized crossover trial where they exercised for 1 h at 40% of Ppeak or remained at rest. Plasma samples were analyzed for R- and S-BAIBA using dual column HPLC-fluorescence. The plasma concentration of baseline R-BAIBA was 67 times higher compared to S-BAIBA (1734 ± 821 vs. 29.3 ± 7.8 nM). Exercise induced a 13 and 20% increase in R-BAIBA and S-BAIBA, respectively. The AGXT2 rs37369 genotype strongly affected baseline levels of R-BAIBA, but did not have an impact on baseline S-BAIBA. We demonstrate that BAIBA should not be treated as one molecule, given (1) the markedly uneven distribution of its enantiomers in human plasma favoring R-BAIBA, and (2) their different metabolic source, as evidenced by the AGXT2 polymorphism only affecting R-BAIBA. The proposed function in organ cross talk is supported by the current data and may apply to both enantiomers, but the tissue of origin remains unclear.

Highlights

Β-aminoisobutyric acid (BAIBA), known as 3-amino-2-methylpropanoic acid, is a nonproteinogenic amino acid
A conceivable possibility would be that the rs37369 single nucleotide polymorphisms (SNPs) induces altered metabolism and accumulation of only R-β-aminoisobutyric acid (BAIBA), as alanine - glyoxylate aminotransferase 2 (AGXT2) is not involved in the S-BAIBA metabolism
The actual 1-h aerobic exercise test was performed at 139 ± 30 Watt, which corresponded to 62 ± 9% of VO2peak and was below each participant’s aerobic threshold, as evaluated with the gas exchange threshold

Summary

Introduction

Β-aminoisobutyric acid (BAIBA), known as 3-amino-2-methylpropanoic acid, is a nonproteinogenic amino acid. Acute Exercise and R-/S-BAIBA overexpressing the exercise-induced transcription factor PGC-1α They established that after 3 weeks, plasma BAIBA concentration increased by 20% in mice having access to a running wheel compared to their sedentary littermates. Potential acute changes of plasma BAIBA in response to exercise, which is a common characteristic of myokines, were not investigated by these authors at that point. Both R- and S-MMSA can be metabolized into propionyl-CoA and further metabolized into the tricarboxylic acid cycle It has been suggested, there is at this point no solid evidence for a spontaneous or enzymatic racemization that might be able to convert R-/S- BAIBA directly or via R-/S- MMSA in healthy humans (Van Gennip et al, 1981; Tamaki et al, 1990; Roe et al, 1998). Some authors reported that R-BAIBA was 20% (Solem et al, 1974), while others reported it to be 53% (Gejyo et al, 1976)

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