Mass spectrometric profiling of oxidized lipid products in human nonalcoholic fatty liver disease and nonalcoholic steatohepatitis[S]
Oxidative stress is a core abnormality responsible for disease progression in nonalcoholic fatty liver disease (NAFLD). However, the pathways that contribute to oxidative damage in vivo are poorly understood. Our aims were to define the circulating profile of lipid oxidation products in NAFLD patien...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2010-10-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520409940 |
| _version_ | 1818726715265908736 |
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| author | Ariel E. Feldstein Rocio Lopez Tarek Abu-Rajab Tamimi Lisa Yerian Yoon-Mi Chung Michael Berk Renliang Zhang Thomas M. McIntyre Stanley L. Hazen |
| author_facet | Ariel E. Feldstein Rocio Lopez Tarek Abu-Rajab Tamimi Lisa Yerian Yoon-Mi Chung Michael Berk Renliang Zhang Thomas M. McIntyre Stanley L. Hazen |
| author_sort | Ariel E. Feldstein |
| collection | DOAJ |
| description | Oxidative stress is a core abnormality responsible for disease progression in nonalcoholic fatty liver disease (NAFLD). However, the pathways that contribute to oxidative damage in vivo are poorly understood. Our aims were to define the circulating profile of lipid oxidation products in NAFLD patients, the source of these products, and assess whether their circulating levels reflect histological changes in the liver. The levels of multiple structurally specific oxidized fatty acids, including individual hydroxy-eicosatetraenoic acids (HETE), hydroxy-octadecadenoic acids (HODE), and oxo-octadecadenoic acids (oxoODE), were measured by mass spectrometry in plasma at time of liver biopsy in an initial cohort of 73 and a validation cohort of 49 consecutive patients. Of the markers monitored, 9- and 13-HODEs and 9- and 13-oxoODEs, products of free radical-mediated oxidation of linoleic acid (LA), were significantly elevated in patients with nonalcoholic steatohepatitis (NASH), compared with patients with steatosis. A strong correlation was revealed between these oxidation products and liver histopathology (inflammation, fibrosis, and steatosis). Further analyses of HODEs showed equivalent R and S chiral distribution. A risk score for NASH (oxNASH) was developed in the initial clinical cohort and shown to have high diagnostic accuracy for NASH versus steatosis in the independent validation cohort. Subjects with elevated oxNASH levels (top tertile) were 9.7-fold (P < 0.0001) more likely to have NASH than those with low levels (bottom tertile). Collectively, these findings support a key role for free radical-mediated linoleic acid oxidation in human NASH and define a risk score, oxNASH, for noninvasive detection of the presence of NASH. |
| first_indexed | 2024-12-17T22:02:36Z |
| format | Article |
| id | doaj.art-af2fc329571c49b1bd69444d4af637f3 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T22:02:36Z |
| publishDate | 2010-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-af2fc329571c49b1bd69444d4af637f32022-12-21T21:30:56ZengElsevierJournal of Lipid Research0022-22752010-10-01511030463054Mass spectrometric profiling of oxidized lipid products in human nonalcoholic fatty liver disease and nonalcoholic steatohepatitis[S]Ariel E. Feldstein0Rocio Lopez1Tarek Abu-Rajab Tamimi2Lisa Yerian3Yoon-Mi Chung4Michael Berk5Renliang Zhang6Thomas M. McIntyre7Stanley L. Hazen8To whom correspondence should be addressed. feldsta@ccf.org; Department of Cell Biology, Lerner Research Institute, Cleveland Clinic College of Medicine, Case Western Reserve University, Cleveland, OH; Center for Cardiovascular Diagnostics Prevention, Cleveland Clinic, Cleveland, OH; Departments of Pediatric Gastroenterology, Cleveland Clinic, Cleveland, OHQuantitative Health Sciences, Cleveland Clinic, Cleveland, OHGastroenterology and Hepatology, Cleveland Clinic, Cleveland, OHAnatomic Pathology, Cleveland Clinic, Cleveland, OHDepartment of Cell Biology, Lerner Research Institute, Cleveland Clinic College of Medicine, Case Western Reserve University, Cleveland, OH; Center for Cardiovascular Diagnostics Prevention, Cleveland Clinic, Cleveland, OHDepartment of Cell Biology, Lerner Research Institute, Cleveland Clinic College of Medicine, Case Western Reserve University, Cleveland, OH; Center for Cardiovascular Diagnostics Prevention, Cleveland Clinic, Cleveland, OHDepartment of Cell Biology, Lerner Research Institute, Cleveland Clinic College of Medicine, Case Western Reserve University, Cleveland, OH; Center for Cardiovascular Diagnostics Prevention, Cleveland Clinic, Cleveland, OHDepartment of Cell Biology, Lerner Research Institute, Cleveland Clinic College of Medicine, Case Western Reserve University, Cleveland, OH; Center for Cardiovascular Diagnostics Prevention, Cleveland Clinic, Cleveland, OHDepartment of Cell Biology, Lerner Research Institute, Cleveland Clinic College of Medicine, Case Western Reserve University, Cleveland, OH; Center for Cardiovascular Diagnostics Prevention, Cleveland Clinic, Cleveland, OH; Cardiovascular Medicine, Cleveland Clinic, Cleveland, OHOxidative stress is a core abnormality responsible for disease progression in nonalcoholic fatty liver disease (NAFLD). However, the pathways that contribute to oxidative damage in vivo are poorly understood. Our aims were to define the circulating profile of lipid oxidation products in NAFLD patients, the source of these products, and assess whether their circulating levels reflect histological changes in the liver. The levels of multiple structurally specific oxidized fatty acids, including individual hydroxy-eicosatetraenoic acids (HETE), hydroxy-octadecadenoic acids (HODE), and oxo-octadecadenoic acids (oxoODE), were measured by mass spectrometry in plasma at time of liver biopsy in an initial cohort of 73 and a validation cohort of 49 consecutive patients. Of the markers monitored, 9- and 13-HODEs and 9- and 13-oxoODEs, products of free radical-mediated oxidation of linoleic acid (LA), were significantly elevated in patients with nonalcoholic steatohepatitis (NASH), compared with patients with steatosis. A strong correlation was revealed between these oxidation products and liver histopathology (inflammation, fibrosis, and steatosis). Further analyses of HODEs showed equivalent R and S chiral distribution. A risk score for NASH (oxNASH) was developed in the initial clinical cohort and shown to have high diagnostic accuracy for NASH versus steatosis in the independent validation cohort. Subjects with elevated oxNASH levels (top tertile) were 9.7-fold (P < 0.0001) more likely to have NASH than those with low levels (bottom tertile). Collectively, these findings support a key role for free radical-mediated linoleic acid oxidation in human NASH and define a risk score, oxNASH, for noninvasive detection of the presence of NASH.http://www.sciencedirect.com/science/article/pii/S0022227520409940oxidized fatty acidsmass spectrometrychiral mass spectrometry |
| spellingShingle | Ariel E. Feldstein Rocio Lopez Tarek Abu-Rajab Tamimi Lisa Yerian Yoon-Mi Chung Michael Berk Renliang Zhang Thomas M. McIntyre Stanley L. Hazen Mass spectrometric profiling of oxidized lipid products in human nonalcoholic fatty liver disease and nonalcoholic steatohepatitis[S] Journal of Lipid Research oxidized fatty acids mass spectrometry chiral mass spectrometry |
| title | Mass spectrometric profiling of oxidized lipid products in human nonalcoholic fatty liver disease and nonalcoholic steatohepatitis[S] |
| title_full | Mass spectrometric profiling of oxidized lipid products in human nonalcoholic fatty liver disease and nonalcoholic steatohepatitis[S] |
| title_fullStr | Mass spectrometric profiling of oxidized lipid products in human nonalcoholic fatty liver disease and nonalcoholic steatohepatitis[S] |
| title_full_unstemmed | Mass spectrometric profiling of oxidized lipid products in human nonalcoholic fatty liver disease and nonalcoholic steatohepatitis[S] |
| title_short | Mass spectrometric profiling of oxidized lipid products in human nonalcoholic fatty liver disease and nonalcoholic steatohepatitis[S] |
| title_sort | mass spectrometric profiling of oxidized lipid products in human nonalcoholic fatty liver disease and nonalcoholic steatohepatitis s |
| topic | oxidized fatty acids mass spectrometry chiral mass spectrometry |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520409940 |
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