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Open AccessArticle

Exploring the Benefit of 2-Methylbutyric Acid in Patients Undergoing Hemodialysis Using a Cardiovascular Proteomics Approach

1
Graduate Institute of Clinical Medicine, College of Medicines, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
2
Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
3
Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
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Department of Medical Sciences, Uppsala University, 752 36 Uppsala, Sweden
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Faculty of Renal Care, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
6
Department of Chemistry, National Taiwan University, Taipei 10617, Taiwan
7
Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
8
Division of General Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
*
Author to whom correspondence should be addressed.
Nutrients 2019, 11(12), 3033; https://doi.org/10.3390/nu11123033
Received: 27 October 2019 / Revised: 14 November 2019 / Accepted: 25 November 2019 / Published: 12 December 2019
Short-chain fatty acids (SCFAs) can reduce pro-inflammatory parameters and oxidative stress, providing potential cardiovascular (CV) benefits. Although some evidence links SCFAs with host metabolic health via several biological mechanisms, the role of SCFA on CV disease in patients with kidney disease remains unclear. Herein, we investigate the association between a SCFA, 2-methylbutyric acid, and target CV proteomics to explore the potential pathophysiology of SCFA-related CV benefit in patients with kidney disease. Circulating 2-methylbutyric acid was quantified by high-performance liquid chromatography and 181 CV proteins by a proximity extension assay in 163 patients undergoing hemodialysis (HD). The associations between 2-methylbutyric acid and CV proteins were evaluated using linear regression analysis with age and gender, and multiple testing adjustment. The selected CV protein in the discovery phase was further confirmed in multivariable-adjusted models and evaluated by continuous scale association. The mean value of circulating 2-methylbutyric acid was 0.22 ± 0.02 µM, which was negatively associated with bone morphogenetic protein 6 (BMP-6) according to the false discovery rate (FDR) multiple testing adjustment method. The 2-methylbutyric acid level remained negatively associated with BMP-6 (β coefficient −1.00, 95% confidence interval −1.45 to −0.55, p < 0.001) after controlling for other CV risk factors in multivariable models. The cubic spline curve demonstrated a linear relationship. In conclusion, circulating 2-methylbutyric acid level was negatively associated with BMP-6, suggesting that this pathway maybe involved in vascular health in patients undergoing HD. However, further in vitro work is still needed to validate the translation of the mechanistic pathways. View Full-Text
Keywords: short-chain fatty acids; 2-methylbutyric acid; target proteomics; bone morphogenetic protein 6; hemodialysis; end-stage renal disease short-chain fatty acids; 2-methylbutyric acid; target proteomics; bone morphogenetic protein 6; hemodialysis; end-stage renal disease
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Wu, P.-H.; Chiu, Y.-W.; Zou, H.-B.; Hsu, C.-C.; Lee, S.-C.; Lin, Y.-T.; Tsai, Y.-C.; Kuo, M.-C.; Hwang, S.-J. Exploring the Benefit of 2-Methylbutyric Acid in Patients Undergoing Hemodialysis Using a Cardiovascular Proteomics Approach. Nutrients 2019, 11, 3033.

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