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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Autores principales:	Emma J. Robinson, Matthew C. Taddeo, Xin Chu, Weixing Shi, Craig Wood, Christopher Still, Virginia G. Rovnyak, David Rovnyak
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	nonalcoholic fatty liver disease NAFLD obesity nuclear magnetic resonance NMR metabolomics Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/b969e8e1bbec4e9e88c9cf0348489cde
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spelling	oai:doaj.org-article:b969e8e1bbec4e9e88c9cf0348489cde2021-11-25T18:20:33ZAqueous Metabolite Trends for the Progression of Nonalcoholic Fatty Liver Disease in Female Bariatric Surgery Patients by Targeted <sup>1</sup>H-NMR Metabolomics10.3390/metabo111107372218-1989https://doaj.org/article/b969e8e1bbec4e9e88c9cf0348489cde2021-10-01T00:00:00Zhttps://www.mdpi.com/2218-1989/11/11/737https://doaj.org/toc/2218-1989Determining 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.Emma J. RobinsonMatthew C. TaddeoXin ChuWeixing ShiCraig WoodChristopher StillVirginia G. RovnyakDavid RovnyakMDPI AGarticlenonalcoholic fatty liver diseaseNAFLDobesitynuclear magnetic resonanceNMRmetabolomicsMicrobiologyQR1-502ENMetabolites, Vol 11, Iss 737, p 737 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	nonalcoholic fatty liver disease NAFLD obesity nuclear magnetic resonance NMR metabolomics Microbiology QR1-502
spellingShingle	nonalcoholic fatty liver disease NAFLD obesity nuclear magnetic resonance NMR metabolomics Microbiology QR1-502 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
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.
format	article
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
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_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_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_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
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/b969e8e1bbec4e9e88c9cf0348489cde
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Aqueous Metabolite Trends for the Progression of Nonalcoholic Fatty Liver Disease in Female Bariatric Surgery Patients by Targeted <sup>1</sup>H-NMR Metabolomics

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