Rapid and Precise Measurement of Serum Branched-Chain and Aromatic Amino Acids by Isotope Dilution Liquid Chromatography Tandem Mass Spectrometry

Yang, Ruiyue; Dong, Jun; Guo, Haoyu; Li, Hongxia; Wang, Shu; Zhao, Haijian; Zhou, Weiyan; Yu, Songlin; Wang, Mo; Chen, Wenxiang

doi:10.1371/journal.pone.0081144

Cited by 31 publications

(38 citation statements)

References 24 publications

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“…Felig and colleagues [23] originally reported that BCAAs and AAAs correlated with obesity and serum insulin. More recent investigations, as well as our previous research, highlighted associations of certain amino acids with obesity, elevated serum glucose, dyslipidemia and high blood pressure [3]–[5], [8], [15]. The present study extends the prior work by demonstrating robust and reproducible associations of circulating levels of BCAAs and AAAs with these previously studied risk factors.…”

Section: Discussionsupporting

confidence: 87%

Association of Branched-Chain Amino Acids with Carotid Intima-Media Thickness and Coronary Artery Disease Risk Factors

et al. 2014

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BackgroundRecent studies have determined that branched-chain (BCAAs) and aromatic (AAAs) amino acids are strongly correlated with obesity and atherogenic dyslipidemia and are strong predictors of diabetes. However, it is not clear if these amino acids are capable of identifying subjects with coronary artery disease (CAD), particularly with subclinical atherosclerosis who are at risk of developing CAD.MethodsFour hundred and seventy two Chinese subjects (272 males and 200 females, 42–97 y of age) undergoing physical exams were recruited at random for participation in the cross-sectional study. Serum BCAAs and AAAs were measured using our previously reported isotope dilution liquid chromatography tandem mass spectrometry method. Bilateral B-mode carotid artery images for carotid intima-media thickness (cIMT) were acquired at end diastole and cIMT values more than 0.9 mm were categorized as increased. Correlations of BCAAs with cIMT and other CAD risk factors were analyzed.ResultsBCAAs and AAAs were significantly and positively associated with risk factors of CAD, e.g., cIMT, BMI, waist circumference, blood pressure, fasting blood glucose, TG, apoB, apoB/apoAI ratio, apoCII, apoCIII and hsCRP, and were significantly and negatively associated with HDL-C and apoAI. Stepwise multiple linear regression analysis revealed that age (β = 0.175, P<0.001), log BCAA (β = 0.147, P<0.001) and systolic blood pressure (β = 0.141, P = 0.012) were positively and independently associated with cIMT. In the logistic regression model, the most and only powerful laboratory factor correlated with increased cIMT was BCAA (the odds ratio of the fourth quartile compared to the first quartile was 2.679; P = 0.009).ConclusionBCAAs are independently correlated with increased cIMT. This correlation would open a new field of research in the mechanistic understanding and risk assessment of CAD.

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Section: Discussionsupporting

confidence: 87%

Association of Branched-Chain Amino Acids with Carotid Intima-Media Thickness and Coronary Artery Disease Risk Factors

et al. 2014

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“…A new longitudinal data in a population-based cohort of nondiabetic British European and South Asian men, followed up for 19 years, concluded that BCAAs and AAAs may be focuses for identifying novel etiological mechanisms and potential treatment targets for diabetes in South Asian populations as they may contribute to their excess risk of diabetes [ 26 ]. Another is that BCAAs are related to other MS components such as elevated WC, elevated TG, and decreased HDL-C in animal and clinical study [ 24 , 36 ]. A recent longitudinal study from Japan showed that plasma-free amino acids profile can predict the four-year risk for developing lifestyle-related diseases, including diabetes, dyslipidemia, and hypertension in a general Japanese population [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Relationship between Branched-Chain Amino Acids, Metabolic Syndrome, and Cardiovascular Risk Profile in a Chinese Population: A Cross-Sectional Study

Wen

Sun

Gong

et al. 2016

International Journal of Endocrinology

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Objective. This study aimed to evaluate the relationship between branched-chain amino acids (BCAAs), metabolic syndrome (MS), and other cardiovascular (CV) risk factors in middle-aged and elderly Chinese population at high risk for the development of cardiovascular disease (CVD). Methods. 1302 subjects were enrolled from the Huai'an Diabetes Prevention Program. Results. BCAAs levels were positively correlated with MS, its components, and CV risk profile. The odds ratio (OR) for MS among subjects in the fourth quartile of BCAAs levels showed a 2.17-fold increase compared with those in the first quartile. BCAAs were independently associated with high Framingham risk score even after adjusting for MS and its components (P < 0.0001). Additionally, the OR for high CV risk was 3.20-fold (P < 0.0001) in participants in the fourth BCAAs quartile with MS compared with participants in the first BCAAs quartile without MS. Conclusions. Increased BCAAs levels are independent risk factors of MS and CVD in addition to the traditional factors in middle-aged and elderly Chinese population. The development of CVD in MS patients with high level BCAAs is accelerated. Intervention studies are needed to investigate whether the strategy of BCAAs reduction has impacts on endpoints in patients with higher CV risk. This study is registered with ChiCTR-TRC-14005029.

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“…High serum branched-chain amino acid (BCAA; isoleucine, leucine, and valine) concentrations have been shown to be predictors or markers of insulin resistance (1), obesity (2, 3), diabetes (4, 5), and atherogenetic dyslipidemia (6, 7) and response to a test meal (8). A 12-year prospective follow-up study of initially normoglycemic individuals showed an association between high serum BCAA levels and incidence of type 2 diabetes (4).…”

Section: Introductionmentioning

confidence: 99%

Branched-Chain Amino Acid Levels Are Related with Surrogates of Disturbed Lipid Metabolism among Older Men

et al. 2016

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Aims/hypothesisExisting studies suggest that decreased branched-chain amino acid (BCAA) catabolism and thus elevated levels in blood are associated with metabolic disturbances. Based on such information, we have developed a hypothesis how BCAA degradation mechanistically connects to tricarboxylic acid cycle, intramyocellular lipid storage, and oxidation, thus allowing more efficient mitochondrial energy production from lipids as well as providing better metabolic health. We analyzed whether data from aged Finnish men are in line with our mechanistic hypothesis linking BCAA catabolism and metabolic disturbances.MethodsOlder Finnish men enriched with individuals having been athletes in young adulthood (n = 593; mean age 72.6 ± 5.9 years) responded to questionnaires, participated in a clinical examination including assessment of body composition with bioimpedance and gave fasting blood samples for various analytes as well as participated in a 2-h 75 g oral glucose tolerance test. Metabolomics measurements from serum included BCAAs (isoleucine, leucine, and valine).ResultsOut of the 593 participants, 59 had previously known type 2 diabetes, further 67 had screen-detected type 2 diabetes, 127 impaired glucose tolerance, and 125 impaired fasting glucose, while 214 had normal glucose regulation and one had missing glucose tolerance information. There were group differences in all of the BCAA concentrations (p ≤ 0.005 for all BCAAs), such that those with normal glucose tolerance had the lowest and those with diabetes mellitus had the highest BCAA concentrations. All BCAA levels correlated positively with body fat percentage (r = 0.29–0.34, p < 0.0001 for all). Expected associations with high BCAA concentrations and unfavorable metabolic profile indicators from metabolomics analysis were found. Except for glucose concentrations, the associations were stronger with isoleucine and leucine than with valine.Conclusion/interpretationThe findings provided further support for our hypothesis by strengthening the idea that the efficiency of BCAA catabolism may be mechanistically involved in the regulation of fat oxidation, thus affecting the levels of metabolic disease risk factors.

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Rapid and Precise Measurement of Serum Branched-Chain and Aromatic Amino Acids by Isotope Dilution Liquid Chromatography Tandem Mass Spectrometry

Cited by 31 publications

References 24 publications

Association of Branched-Chain Amino Acids with Carotid Intima-Media Thickness and Coronary Artery Disease Risk Factors

Association of Branched-Chain Amino Acids with Carotid Intima-Media Thickness and Coronary Artery Disease Risk Factors

Relationship between Branched-Chain Amino Acids, Metabolic Syndrome, and Cardiovascular Risk Profile in a Chinese Population: A Cross-Sectional Study

Branched-Chain Amino Acid Levels Are Related with Surrogates of Disturbed Lipid Metabolism among Older Men

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