Distinguishing NASH Histological Severity Using a Multiplatform Metabolomics Approach
Nonalcoholic fatty liver disease (NAFLD) is categorized based on histological severity into nonalcoholic fatty liver (NAFL) or nonalcoholic steatohepatitis (NASH). We used a multiplatform metabolomics approach to identify metabolite markers and metabolic pathways that distinguish NAFL from early NAS...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-04-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/10/4/168 |
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| author | George N. Ioannou G. A. Nagana Gowda Danijel Djukovic Daniel Raftery |
| author_facet | George N. Ioannou G. A. Nagana Gowda Danijel Djukovic Daniel Raftery |
| author_sort | George N. Ioannou |
| collection | DOAJ |
| description | Nonalcoholic fatty liver disease (NAFLD) is categorized based on histological severity into nonalcoholic fatty liver (NAFL) or nonalcoholic steatohepatitis (NASH). We used a multiplatform metabolomics approach to identify metabolite markers and metabolic pathways that distinguish NAFL from early NASH and advanced NASH. We analyzed fasting serum samples from 57 prospectively-recruited patients with histologically-proven NAFLD, including 12 with NAFL, 31 with early NASH and 14 with advanced NASH. Metabolite profiling was performed using a combination of liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) spectroscopy analyzed with multivariate statistical and pathway analysis tools. We targeted 237 metabolites of which 158 were quantified. Multivariate analysis uncovered metabolite profile clusters for patients with NAFL, early NASH, and advanced NASH. Also, multiple individual metabolites were associated with histological severity, most notably spermidine which was more than 2-fold lower in advanced fibrosis vs. early fibrosis, in advanced NASH vs. NAFL and in advanced NASH vs. early NASH, suggesting that spermidine exercises a protective effect against development of fibrosing NASH. Furthermore, the results also showed metabolic pathway perturbations between early-NASH and advanced-NASH. In conclusion, using a combination of two reliable analytical platforms (LC-MS and NMR spectroscopy) we identified individual metabolites, metabolite clusters and metabolic pathways that were significantly different between NAFL, early-NASH, and advanced-NASH. These differences provide mechanistic insights as well as potentially important metabolic biomarker candidates that may noninvasively distinguish patients with NAFL, early-NASH, and advanced-NASH. The associations of spermidine levels with less advanced histology merit further assessment of the potential protective effects of spermidine in NAFLD. |
| first_indexed | 2024-03-10T20:15:30Z |
| format | Article |
| id | doaj.art-7084863ed53d477e87f160385e9ec8e9 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-10T20:15:30Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-7084863ed53d477e87f160385e9ec8e92023-11-19T22:34:48ZengMDPI AGMetabolites2218-19892020-04-0110416810.3390/metabo10040168Distinguishing NASH Histological Severity Using a Multiplatform Metabolomics ApproachGeorge N. Ioannou0G. A. Nagana Gowda1Danijel Djukovic2Daniel Raftery3Division of Gastroenterology, Veterans Affairs Puget Sound Healthcare System and University of Washington, Seattle, WA 98108, USANorthwest Metabolomics Research Center, Anesthesiology and Pain Medicine, University of Washington, Seattle, WA 98109, USANorthwest Metabolomics Research Center, Anesthesiology and Pain Medicine, University of Washington, Seattle, WA 98109, USANorthwest Metabolomics Research Center, Anesthesiology and Pain Medicine, University of Washington, Seattle, WA 98109, USANonalcoholic fatty liver disease (NAFLD) is categorized based on histological severity into nonalcoholic fatty liver (NAFL) or nonalcoholic steatohepatitis (NASH). We used a multiplatform metabolomics approach to identify metabolite markers and metabolic pathways that distinguish NAFL from early NASH and advanced NASH. We analyzed fasting serum samples from 57 prospectively-recruited patients with histologically-proven NAFLD, including 12 with NAFL, 31 with early NASH and 14 with advanced NASH. Metabolite profiling was performed using a combination of liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) spectroscopy analyzed with multivariate statistical and pathway analysis tools. We targeted 237 metabolites of which 158 were quantified. Multivariate analysis uncovered metabolite profile clusters for patients with NAFL, early NASH, and advanced NASH. Also, multiple individual metabolites were associated with histological severity, most notably spermidine which was more than 2-fold lower in advanced fibrosis vs. early fibrosis, in advanced NASH vs. NAFL and in advanced NASH vs. early NASH, suggesting that spermidine exercises a protective effect against development of fibrosing NASH. Furthermore, the results also showed metabolic pathway perturbations between early-NASH and advanced-NASH. In conclusion, using a combination of two reliable analytical platforms (LC-MS and NMR spectroscopy) we identified individual metabolites, metabolite clusters and metabolic pathways that were significantly different between NAFL, early-NASH, and advanced-NASH. These differences provide mechanistic insights as well as potentially important metabolic biomarker candidates that may noninvasively distinguish patients with NAFL, early-NASH, and advanced-NASH. The associations of spermidine levels with less advanced histology merit further assessment of the potential protective effects of spermidine in NAFLD.https://www.mdpi.com/2218-1989/10/4/168nonalcoholic fatty livernonalcoholic steatohepatitisliquid chromatography-mass spectrometrynuclear magnetic resonance spectroscopymetabolic pathway |
| spellingShingle | George N. Ioannou G. A. Nagana Gowda Danijel Djukovic Daniel Raftery Distinguishing NASH Histological Severity Using a Multiplatform Metabolomics Approach Metabolites nonalcoholic fatty liver nonalcoholic steatohepatitis liquid chromatography-mass spectrometry nuclear magnetic resonance spectroscopy metabolic pathway |
| title | Distinguishing NASH Histological Severity Using a Multiplatform Metabolomics Approach |
| title_full | Distinguishing NASH Histological Severity Using a Multiplatform Metabolomics Approach |
| title_fullStr | Distinguishing NASH Histological Severity Using a Multiplatform Metabolomics Approach |
| title_full_unstemmed | Distinguishing NASH Histological Severity Using a Multiplatform Metabolomics Approach |
| title_short | Distinguishing NASH Histological Severity Using a Multiplatform Metabolomics Approach |
| title_sort | distinguishing nash histological severity using a multiplatform metabolomics approach |
| topic | nonalcoholic fatty liver nonalcoholic steatohepatitis liquid chromatography-mass spectrometry nuclear magnetic resonance spectroscopy metabolic pathway |
| url | https://www.mdpi.com/2218-1989/10/4/168 |
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