Aqueous Metabolite Trends for the Progression of Nonalcoholic Fatty Liver Disease in Female Bariatric Surgery Patients by Targeted <sup>1</sup>H-NMR Metabolomics
Determining biomarkers and better characterizing the biochemical progression of nonalcoholic fatty liver disease (NAFLD) remains a clinical challenge. A targeted <sup>1</sup>H-NMR study of serum, combined with clinical variables, detected and localized biomarkers to stages of NAFLD in mo...
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MDPI AG
2021-10-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/11/11/737 |
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| author | Emma J. Robinson Matthew C. Taddeo Xin Chu Weixing Shi Craig Wood Christopher Still Virginia G. Rovnyak David Rovnyak |
| author_facet | Emma J. Robinson Matthew C. Taddeo Xin Chu Weixing Shi Craig Wood Christopher Still Virginia G. Rovnyak David Rovnyak |
| author_sort | Emma J. Robinson |
| collection | DOAJ |
| description | Determining biomarkers and better characterizing the biochemical progression of nonalcoholic fatty liver disease (NAFLD) remains a clinical challenge. A targeted <sup>1</sup>H-NMR study of serum, combined with clinical variables, detected and localized biomarkers to stages of NAFLD in morbidly obese females. Pre-surgery serum samples from 100 middle-aged, morbidly obese female subjects, grouped on gold-standard liver wedge biopsies (non-NAFLD; steatosis; and fibrosis) were collected, extracted, and analyzed in aqueous (D<sub>2</sub>O) buffer (<sup>1</sup>H, 600 MHz). Profiled concentrations were subjected to exploratory statistical analysis. Metabolites varying significantly between the non-NAFLD and steatosis groups included the ketone bodies 3-hydroxybutyrate (↓; <i>p</i> = 0.035) and acetone (↓; <i>p</i> = 0.012), and also alanine (↑; <i>p</i> = 0.004) and a putative pyruvate signal (↑; <i>p</i> = 0.003). In contrast, the steatosis and fibrosis groups were characterized by 2-hydroxyisovalerate (↑; <i>p</i> = 0.023), betaine (↓; <i>p</i> = 0.008), hypoxanthine (↓; <i>p</i> = 0.003), taurine (↓; <i>p</i> = 0.001), 2-hydroxybutyrate (↑; <i>p</i> = 0.045), 3-hydroxyisobutyrate (↑; <i>p</i> = 0.046), and increasing medium chain fatty acids. Exploratory classification models with and without clinical variables exhibited overall success rates ca. 75–85%. In the study conditions, inhibition of fatty acid oxidation and disruption of the hepatic urea cycle are supported as early features of NAFLD that continue in fibrosis. In fibrosis, markers support inflammation, hepatocyte damage, and decreased liver function. Complementarity of NMR concentrations and clinical information in classification models is shown. A broader hypothesis that standard-of-care sera can yield metabolomic information is supported. |
| first_indexed | 2024-03-10T05:17:04Z |
| format | Article |
| id | doaj.art-b969e8e1bbec4e9e88c9cf0348489cde |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-10T05:17:04Z |
| publishDate | 2021-10-01 |
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| series | Metabolites |
| spelling | doaj.art-b969e8e1bbec4e9e88c9cf0348489cde2023-11-23T00:20:47ZengMDPI AGMetabolites2218-19892021-10-01111173710.3390/metabo11110737Aqueous Metabolite Trends for the Progression of Nonalcoholic Fatty Liver Disease in Female Bariatric Surgery Patients by Targeted <sup>1</sup>H-NMR MetabolomicsEmma J. Robinson0Matthew C. Taddeo1Xin Chu2Weixing Shi3Craig Wood4Christopher Still5Virginia G. Rovnyak6David Rovnyak7Department of Chemistry, Bucknell University, 1 Dent Drive, Lewisburg, PA 17837, USADepartment of Chemistry, Bucknell University, 1 Dent Drive, Lewisburg, PA 17837, USAThe Obesity Institute, Geisinger, Danville, PA 17822, USAThe Obesity Institute, Geisinger, Danville, PA 17822, USAThe Obesity Institute, Geisinger, Danville, PA 17822, USAThe Obesity Institute, Geisinger, Danville, PA 17822, USAUniversity of Virginia School of Nursing, Charlottesville, VA 22908, USADepartment of Chemistry, Bucknell University, 1 Dent Drive, Lewisburg, PA 17837, USADetermining biomarkers and better characterizing the biochemical progression of nonalcoholic fatty liver disease (NAFLD) remains a clinical challenge. A targeted <sup>1</sup>H-NMR study of serum, combined with clinical variables, detected and localized biomarkers to stages of NAFLD in morbidly obese females. Pre-surgery serum samples from 100 middle-aged, morbidly obese female subjects, grouped on gold-standard liver wedge biopsies (non-NAFLD; steatosis; and fibrosis) were collected, extracted, and analyzed in aqueous (D<sub>2</sub>O) buffer (<sup>1</sup>H, 600 MHz). Profiled concentrations were subjected to exploratory statistical analysis. Metabolites varying significantly between the non-NAFLD and steatosis groups included the ketone bodies 3-hydroxybutyrate (↓; <i>p</i> = 0.035) and acetone (↓; <i>p</i> = 0.012), and also alanine (↑; <i>p</i> = 0.004) and a putative pyruvate signal (↑; <i>p</i> = 0.003). In contrast, the steatosis and fibrosis groups were characterized by 2-hydroxyisovalerate (↑; <i>p</i> = 0.023), betaine (↓; <i>p</i> = 0.008), hypoxanthine (↓; <i>p</i> = 0.003), taurine (↓; <i>p</i> = 0.001), 2-hydroxybutyrate (↑; <i>p</i> = 0.045), 3-hydroxyisobutyrate (↑; <i>p</i> = 0.046), and increasing medium chain fatty acids. Exploratory classification models with and without clinical variables exhibited overall success rates ca. 75–85%. In the study conditions, inhibition of fatty acid oxidation and disruption of the hepatic urea cycle are supported as early features of NAFLD that continue in fibrosis. In fibrosis, markers support inflammation, hepatocyte damage, and decreased liver function. Complementarity of NMR concentrations and clinical information in classification models is shown. A broader hypothesis that standard-of-care sera can yield metabolomic information is supported.https://www.mdpi.com/2218-1989/11/11/737nonalcoholic fatty liver diseaseNAFLDobesitynuclear magnetic resonanceNMRmetabolomics |
| spellingShingle | Emma J. Robinson Matthew C. Taddeo Xin Chu Weixing Shi Craig Wood Christopher Still Virginia G. Rovnyak David Rovnyak Aqueous Metabolite Trends for the Progression of Nonalcoholic Fatty Liver Disease in Female Bariatric Surgery Patients by Targeted <sup>1</sup>H-NMR Metabolomics Metabolites nonalcoholic fatty liver disease NAFLD obesity nuclear magnetic resonance NMR metabolomics |
| title | Aqueous Metabolite Trends for the Progression of Nonalcoholic Fatty Liver Disease in Female Bariatric Surgery Patients by Targeted <sup>1</sup>H-NMR Metabolomics |
| title_full | Aqueous Metabolite Trends for the Progression of Nonalcoholic Fatty Liver Disease in Female Bariatric Surgery Patients by Targeted <sup>1</sup>H-NMR Metabolomics |
| title_fullStr | Aqueous Metabolite Trends for the Progression of Nonalcoholic Fatty Liver Disease in Female Bariatric Surgery Patients by Targeted <sup>1</sup>H-NMR Metabolomics |
| title_full_unstemmed | Aqueous Metabolite Trends for the Progression of Nonalcoholic Fatty Liver Disease in Female Bariatric Surgery Patients by Targeted <sup>1</sup>H-NMR Metabolomics |
| title_short | Aqueous Metabolite Trends for the Progression of Nonalcoholic Fatty Liver Disease in Female Bariatric Surgery Patients by Targeted <sup>1</sup>H-NMR Metabolomics |
| title_sort | aqueous metabolite trends for the progression of nonalcoholic fatty liver disease in female bariatric surgery patients by targeted sup 1 sup h nmr metabolomics |
| topic | nonalcoholic fatty liver disease NAFLD obesity nuclear magnetic resonance NMR metabolomics |
| url | https://www.mdpi.com/2218-1989/11/11/737 |
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