| Autor: |
Cheng S; Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China., Wu T; Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China., Yu CQ; Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing 100191, China Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing 100191, China., Sun DJY; Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing 100191, China Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing 100191, China., Pei P; Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing 100191, China., Du HD; Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, United Kingdom., Chen JS; China National Center for Food Safety Risk Assessment, Beijing 100022, China., Chen ZM; Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, United Kingdom., Pang YJ; Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing 100191, China Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing 100191, China., Lyu J; Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing 100191, China Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing 100191, China., Li LM; Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing 100191, China Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing 100191, China. |
| Abstrakt: |
Objective: To explore the relationship between BMI and levels of plasma amino acids and acylcarnitines in Chinese adults. Methods: Based on 2 182 individuals with targeted mass spectrometry metabolomic measurements from the first resurvey of the China Kadoorie Biobank, we assessed the linear and nonlinear associations between BMI and plasma levels of 20 amino acids and 40 acylcarnitines using linear regression models and restricted cubic spline models, and identified BMI-related metabolic pathways. We conducted one-sample Mendelian randomization (MR) with BMI genetic risk scores as the instrumental variable further to explore the potential causal relationships between BMI and 20 amino acids and 40 acylcarnitines, and tested for horizontal pleiotropy using the MR-Egger method. Results: Observational analyses found that BMI was associated with increased plasma levels of 3 branched-chain amino acids (isoleucine, leucine, and valine), 2 aromatic amino acids (phenylalanine and tyrosine), 3 other amino acids (cysteine, glutamate, lysine), and 7 acylcarnitines (C3, C4, C5, C10, C10:1, C14, and C16), and with decreased circulating levels of asparagine, serine, and glycine. Pathway analysis identified 7 BMI-related amino acids metabolic pathways (false discovery rate corrected all P <0.05), including branched-chain amino acids and aromatic amino acids biosynthesis, glutathione metabolism, etc . BMI showed a nonlinear relationship with leucine, valine, and threonine, and a linear relationship with other amino acids and acylcarnitines. One-sample MR analyses revealed that BMI was associated with elevated levels of tyrosine and 4 acylcarnitines [C5-DC(C6-OH), C5-M-DC, C12-DC, and C14], with tyrosine and acylcarnitine C14 positively correlated with BMI in both observational [the β values (95% CI s) were 0.057 (0.044-0.070) and 0.018 (0.005-0.032), respectively] and One-sample MR analyses [the β values (95% CI s) were 0.102 (0.035-0.169) and 0.104 (0.036-0.173), respectively]. The MR analyses of the current study satisfied the 3 core assumptions of instrumental variable. Conclusions: BMI was associated with circulating 11 amino acids and 7 acylcarnitines in Chinese adults, involving several pathways such as branched-chain amino acid and aromatic amino acid metabolism, fatty acid metabolism, and oxidative stress. There may be a causal relationship between BMI and tyrosine and acylcarnitine C14. |
