Aqueous Metabolite Trends for the Progression of Nonalcoholic Fatty Liver Disease in Female Bariatric Surgery Patients by Targeted 1H-NMR Metabolomics

Authors

Emma J. Robinson, Bucknell UniversityFollow
Matthew C. Taddeo, Bucknell UniversityFollow
Xin Chu, Geisinger, The Obesity InstituteFollow
Weixing Shi, Geisinger, The Obesity InstituteFollow
Craig Wood, Geisinger, The Obesity InstituteFollow
Christopher Still, Geisinger, The Obesity InstituteFollow
Virginia Rovnyak, University of Virginia School of NursingFollow
David Rovnyak, Bucknell UniversityFollow

Publication Date

10-2021

Description

Determining biomarkers and better characterizing the biochemical progression of nonalcoholic fatty liver disease (NAFLD) remains a clinical challenge. A targeted ¹H-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 (D₂O) buffer (¹H, 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 (↓; p = 0.035) and acetone (↓; p = 0.012), and also alanine (↑; p = 0.004) and a putative pyruvate signal (↑; p = 0.003). In contrast, the steatosis and fibrosis groups were characterized by 2-hydroxyisovalerate (↑; p = 0.023), betaine (↓; p = 0.008), hypoxanthine (↓; p = 0.003), taurine (↓; p = 0.001), 2-hydroxybutyrate (↑; p = 0.045), 3-hydroxyisobutyrate (↑; p = 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.

Journal

Metabolites

Volume

11

Issue

11

First Page

737

Last Page

756

Department

Chemistry

Second Department

Cell Biology/Biochemistry

Open Access

Link to OA full text

Link to Published Version

https://www.mdpi.com/2218-1989/11/11/737

DOI

doi.org/10.3390/metabo11110737

Recommended Citation

Robinson, Emma J.; Taddeo, Matthew C.; Chu, Xin; Shi, Weixing; Wood, Craig; Still, Christopher; Rovnyak, Virginia; and Rovnyak, David. "Aqueous Metabolite Trends for the Progression of Nonalcoholic Fatty Liver Disease in Female Bariatric Surgery Patients by Targeted 1H-NMR Metabolomics." (2021) : 737-756.