Quantification of aminobutyric acids and their clinical applications as biomarkers for osteoporosis

Abstract

Osteoporosis is a highly prevalent chronic aging-related disease that frequently is only detected after fracture. We hypothesized that aminobutyric acids could serve as biomarkers for osteoporosis. We developed a quick, accurate, and sensitive screening method for aminobutyric acid isomers and enantiomers yielding correlations with bone mineral density (BMD) and osteoporotic fracture. In serum, γ-aminobutyric acid (GABA) and (R)-3-aminoisobutyric acid (D-BAIBA) have positive associations with physical activity in young lean women. D-BAIBA positively associated with hip BMD in older individuals without osteoporosis/osteopenia. Lower levels of GABA were observed in 60-80 year old women with osteoporotic fractures. Single nucleotide polymorphisms in seven genes related to these metabolites associated with BMD and osteoporosis. In peripheral blood monocytes, dihydropyrimidine dehydrogenase, an enzyme essential to D-BAIBA generation, exhibited positive association with physical activity and hip BMD. Along with their signaling roles, BAIBA and GABA might serve as biomarkers for diagnosis and treatments of osteoporosis.

Bone and Muscle Crosstalk in Aging

“…et al, 2018 ). Recently, Wang et al (2020) illustrate that BAIBA is positively associated with BMD in young, healthy women. The correlation is disrupted after the occurrence of a fracture or during an obese state, mainly due to interference caused by medical treatments and cytokines released by obese subjects.…”

Gamma Aminobutyric Acid-Enriched Fermented Oyster (Crassostrea gigas) Increases the Length of the Growth Plate on the Proximal Tibia Bone in Sprague-Dawley Rats

“…Numerous studies have demonstrated that GABA-enriched functional food have physiological benefits such as suppression of blood pressure [ 22 ], hepatoprotection [ 23 ], decrease in gut inflammation [ 24 ], and regulation of glucose tolerance [ 25 ]. Furthermore, several reports have demonstrated that GABA promoted bone health [ 15 , 16 , 26 , 27 , 28 ]. Watanabe et al [ 26 ] reported that GABA directly regulates the muscle tone, and Muhammad et al [ 27 ] suggested GABA promotes osteoblastogenesis by stimulation of bone formation genes.…”

“…We recently demonstrated that fermentation of oyster by Lactobacillus brevis BJ20 increased the amount of gamma aminobutyric acid (GABA), which may contribute to increased height in Sprague-Dawley (SD) rats [ 12 ]. GABA is associated with bone health and might be a biomarker of osteoporosis diagnosis and therapy [ 16 ]. According to a recent report, high levels of serum GABA were observed in young women, which plays a positive role in physical activity, whereas GABA levels were lower in elderly women with osteoporotic fractures [ 16 ].…”

“…GABA is associated with bone health and might be a biomarker of osteoporosis diagnosis and therapy [ 16 ]. According to a recent report, high levels of serum GABA were observed in young women, which plays a positive role in physical activity, whereas GABA levels were lower in elderly women with osteoporotic fractures [ 16 ]. Our previous study suggested that FO has rich GABA content and increases body length and hepatic insulin-like growth factor-1 (IGF-1) synthesis [ 12 ].…”

Ionic Silicon Protects Oxidative Damage and Promotes Skeletal Muscle Cell Regeneration

“…Aminobutyric acid concentrations were determined using LC-MS/MS analysis, performed on a Shimadzu LCMS-8050 triple quadrupole mass spectrometer (Shimadzu Scientific Instruments Inc., Tokyo, Japan) at the Shimadzu Center at the University of Texas at Arlington. Analysis was performed based on a previously published LC-MS/MS method that enables baseline separation with sensitive detection of aminobutyric acid isomers in minimal amounts of biological fluid samples developed by the Brotto Research Laboratory [ 79 ].…”