Differential Intrahepatic Phospholipid Zonation in Simple Steatosis and Nonalcoholic Steatohepatitis

Wattacheril, Julia; Seeley, Erin H.; Angel, Peggi; Chen, Heidi; Bowen, Benjamin P.; Lanciault, Christian; M.Caprioli, Richard; Abumrad, Naji; Flynn, Charles Robb

doi:10.1371/journal.pone.0057165

Differential Intrahepatic Phospholipid Zonation in Simple Steatosis and Nonalcoholic Steatohepatitis

Journal Article · Mon Feb 25 00:00:00 EST 2013 · PLoS ONE

DOI:https://doi.org/10.1371/journal.pone.0057165· OSTI ID:1627588

Wattacheril, Julia ^[1]; Seeley, Erin H. ^[2]; Angel, Peggi ^[2]; Chen, Heidi ^[2]; Bowen, Benjamin P. ^[3]; Lanciault, Christian ^[2]; M.Caprioli, Richard ^[2]; Abumrad, Naji ^[2]; Flynn, Charles Robb ^[2]

Columbia University, New York, NY (United States); DOE/OSTI
Vanderbilt University, Nashville, TN (United States)
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Nonalcoholic fatty liver disease (NAFLD) occurs frequently in a setting of obesity, dyslipidemia and insulin resistance, but the etiology of the disease, particularly the events favoring progression to nonalcoholic steatohepatitis (NASH) as opposed to simple steatosis (SS), are not fully understood. Based on known zonation patterns in protein, glucose and lipid metabolism, coupled with evidence that phosphatidylcholine may play a role in NASH pathogenesis, we hypothesized that phospholipid zonation exists in liver and that specific phospholipid abundance and distribution may be associated with histologic disease. A survey of normal hepatic protein expression profiles in the Human Protein Atlas revealed pronounced zonation of enzymes involved in lipid utilization and storage, particularly those facilitating phosphatidylcholine (PC) metabolism. Immunohistochemistry of obese normal, SS and NASH liver specimens with anti-phosphatidylethanomine Nmethyltransferase (PEMT) antibodies showed a progressive decrease in the zonal distribution of this PC biosynthetic enzyme. Phospholipid quantitation by liquid chromatography mass spectrometry (LC-MS) in hepatic extracts of Class III obese patients with increasing NAFLD severity revealed that most PC species with 32, 34 and 36 carbons as well as total PC abundance was decreased with SS and NASH. Matrix assisted laser desorption ionization - imaging mass spectrometry (MALDI-IMS) imaging revealed strong zonal distributions for 32, 34 and 36 carbon PCs in controls (minimal histologic findings) and SS that was lost in NASH specimens. Specific lipid species such as PC 34:1 and PC 36:2 best illustrated this phenomenon. These findings suggest that phospholipid zonation may be associated with the presence of an intrahepatic proinflammatory phenotype and thus have broad implications in the etiopathogenesis of NASH.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: National Institutes of Health (NIH); USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1627588

Journal Information:: PLoS ONE, Journal Name: PLoS ONE Journal Issue: 2 Vol. 8; ISSN 1932-6203

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

References (59)

Oxygen: Modulator of metabolic zonation and disease of the liver Jungermann, Kurt; Kietzmann, Thomas Hepatology, Vol. 31, Issue 2 https://doi.org/10.1002/hep.510310201	journal	February 2000
Shotgun lipidomics: Electrospray ionization mass spectrometric analysis and quantitation of cellular lipidomes directly from crude extracts of biological samples Han, Xianlin; Gross, Richard W. Mass Spectrometry Reviews, Vol. 24, Issue 3 https://doi.org/10.1002/mas.20023	journal	January 2005
Improved peak detection and quantification of mass spectrometry data acquired from surface-enhanced laser desorption and ionization by denoising spectra with the undecimated discrete wavelet transform Coombes, Kevin R.; Tsavachidis, Spiridon; Morris, Jeffrey S. PROTEOMICS, Vol. 5, Issue 16 https://doi.org/10.1002/pmic.200401261	journal	November 2005
Detection of Individual Phospholipids in Lipid Mixtures by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry: Phosphatidylcholine Prevents the Detection of Further Species Petković, Marijana; Schiller, Jürgen; Müller, Matthias Analytical Biochemistry, Vol. 289, Issue 2 https://doi.org/10.1006/abio.2000.4926	journal	February 2001
Quantitative analysis of regenerating and degenerating areas within the lobule of the carbon tetrachloride-injured liver Morrison, George R.; Brock, Frances E.; Karl, Irene E. Archives of Biochemistry and Biophysics, Vol. 111, Issue 2 https://doi.org/10.1016/0003-9861(65)90208-0	journal	August 1965
Metabolic zonation of the liver: Regulation and implications for liver function Gebhardt, Rolf Pharmacology & Therapeutics, Vol. 53, Issue 3 https://doi.org/10.1016/0163-7258(92)90055-5	journal	January 1992
Transcription dynamics in a physiological process: β-Catenin signaling directs liver metabolic zonation Torre, Cyril; Perret, Christine; Colnot, Sabine The International Journal of Biochemistry & Cell Biology, Vol. 43, Issue 2 https://doi.org/10.1016/j.biocel.2009.11.004	journal	February 2011
The ratio of phosphatidylcholine to phosphatidylethanolamine influences membrane integrity and steatohepatitis Li, Zhaoyu; Agellon, Luis B.; Allen, Theresa M. Cell Metabolism, Vol. 3, Issue 5 https://doi.org/10.1016/j.cmet.2006.03.007	journal	May 2006
Sublimation as a method of matrix application for mass spectrometric imaging Hankin, Joseph A.; Barkley, Robert M.; Murphy, Robert C. Journal of the American Society for Mass Spectrometry, Vol. 18, Issue 9 https://doi.org/10.1016/j.jasms.2007.06.010	journal	September 2007
Enhancement of protein sensitivity for MALDI imaging mass spectrometry after chemical treatment of tissue sections Seeley, Erin H.; Oppenheimer, Stacey R.; Mi, Deming Journal of the American Society for Mass Spectrometry, Vol. 19, Issue 8 https://doi.org/10.1016/j.jasms.2008.03.016	journal	August 2008
Nutritional assessment and hepatic fatty acid composition in non-alcoholic fatty liver disease (NAFLD): A cross-sectional study Allard, Johane P.; Aghdassi, Elaheh; Mohammed, Saira Journal of Hepatology, Vol. 48, Issue 2 https://doi.org/10.1016/j.jhep.2007.09.009	journal	February 2008
Hepatocellular expression of glutamine synthetase: An indicator of morphogen actions as master regulators of zonation in adult liver Gebhardt, Rolf; Baldysiak-Figiel, Alicja; Krügel, Vera Progress in Histochemistry and Cytochemistry, Vol. 41, Issue 4 https://doi.org/10.1016/j.proghi.2006.12.001	journal	April 2007
Phosphatidylethanolamine N-methyltransferase from liver Vance, Dennis E.; Walkey, Christopher J.; Cui, Zheng Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, Vol. 1348, Issue 1-2 https://doi.org/10.1016/s0005-2760(97)00108-2	journal	September 1997
Increased hepatocyte CYP2E1 expression in a rat nutritional model of hepatic steatosis with inflammation Weltman, Md; Farrell, Gc; Liddle, C. Gastroenterology, Vol. 111, Issue 6 https://doi.org/10.1016/s0016-5085(96)70028-8	journal	December 1996
Kinetic analyses of liver phosphatidylcholine and phosphatidylethanolamine biosynthesis using 13C NMR spectroscopy Reo, N. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, Vol. 1580, Issue 2-3 https://doi.org/10.1016/s1388-1981(01)00202-5	journal	February 2002
Comprehensive LC−MS ^E Lipidomic Analysis using a Shotgun Approach and Its Application to Biomarker Detection and Identification in Osteoarthritis Patients Castro-Perez, Jose M.; Kamphorst, Jurre; DeGroot, Jeroen Journal of Proteome Research, Vol. 9, Issue 5 https://doi.org/10.1021/pr901094j	journal	May 2010
Biosynthesis of phosphatidylethanolamines and phosphatidylcholines from ethanolamine and choline in rat liver Sundler, R.; Akesson, B. Biochemical Journal, Vol. 146, Issue 2 https://doi.org/10.1042/bj1460309	journal	February 1975
Glucagon regulation of gluconeogenesis and ketogenesis in periportal and perivenous rat hepatocytes. Heterogeneity of hormone action and of the mitochondrial redox state Tosh, D.; Alberti, G. M. M.; Agius, L. Biochemical Journal, Vol. 256, Issue 1 https://doi.org/10.1042/bj2560197	journal	November 1988
Zonation of fatty acid metabolism in rat liver Guzmán, M.; Castro, J. Biochemical Journal, Vol. 264, Issue 1 https://doi.org/10.1042/bj2640107	journal	November 1989
Increase in long-chain polyunsaturated fatty acid n−6/n−3 ratio in relation to hepatic steatosis in patients with non-alcoholic fatty liver disease Araya, Julia; Rodrigo, Ramón; Videla, Luis A. Clinical Science, Vol. 106, Issue 6 https://doi.org/10.1042/cs20030326	journal	June 2004
Triglyceride accumulation protects against fatty acid-induced lipotoxicity Listenberger, L. L.; Han, X.; Lewis, S. E. Proceedings of the National Academy of Sciences, Vol. 100, Issue 6 https://doi.org/10.1073/pnas.0630588100	journal	March 2003
Molecular Distinction of Phosphatidylcholine Synthesis between the CDP-Choline Pathway and Phosphatidylethanolamine Methylation Pathway DeLong, Cynthia J.; Shen, You-Jun; Thomas, Michael J. Journal of Biological Chemistry, Vol. 274, Issue 42 https://doi.org/10.1074/jbc.274.42.29683	journal	October 1999
Effect of Anaplerotic Fluxes and Amino Acid Availability on Hepatic Lipoapoptosis Noguchi, Yasushi; Young, Jamey D.; Aleman, Jose O. Journal of Biological Chemistry, Vol. 284, Issue 48 https://doi.org/10.1074/jbc.m109.049478	journal	November 2009
The Membrane Lipid Phosphatidylcholine Is an Unexpected Source of Triacylglycerol in the Liver van der Veen, Jelske N.; Lingrell, Susanne; Vance, Dennis E. Journal of Biological Chemistry, Vol. 287, Issue 28 https://doi.org/10.1074/jbc.m112.381723	journal	July 2012
Targeted Deletion of Hepatic CTP:phosphocholine Cytidylyltransferase α in Mice Decreases Plasma High Density and Very Low Density Lipoproteins Jacobs, René L.; Devlin, Cecilia; Tabas, Ira Journal of Biological Chemistry, Vol. 279, Issue 45 https://doi.org/10.1074/jbc.m404027200	journal	November 2004
Hepatic CTP:Phosphocholine Cytidylyltransferase-α Is a Critical Predictor of Plasma High Density Lipoprotein and Very Low Density Lipoprotein Jacobs, René L.; Lingrell, Susanne; Zhao, Yang Journal of Biological Chemistry, Vol. 283, Issue 4 https://doi.org/10.1074/jbc.m706628200	journal	January 2008
A novel comprehensive wave-form MS data processing method Chen, Shuo; Li, Ming; Hong, Don Bioinformatics, Vol. 25, Issue 6 https://doi.org/10.1093/bioinformatics/btp060	journal	January 2009
Differential gene expression in periportal and perivenous mouse hepatocytes Braeuning, Albert; Ittrich, Carina; Köhle, Christoph FEBS Journal, Vol. 273, Issue 22 https://doi.org/10.1111/j.1742-4658.2006.05503.x	journal	November 2006
Zonation of Parenchymal and Nonparenchymal Metabolism in Liver Jungermann, Kurt; Keitzmann, Thomas Annual Review of Nutrition, Vol. 16, Issue 1 https://doi.org/10.1146/annurev.nu.16.070196.001143	journal	July 1996
Hepatocyte Heterogeneity in the Metabolism of Fatty Acids: Discrepancies on Zonation of Acetyl-CoA Carboxylase Quistorff, Bjorn; Katz, Norbert; Witters, Lee A. Enzyme, Vol. 46, Issue 1-3 https://doi.org/10.1159/000468778	journal	January 1992
Hepatocyte Heterogeneity in the Metabolism of Amino Acids and Ammonia Häussinger, Dieter; Lames, Wouter H.; Moorman, Antoon F. M. Enzyme, Vol. 46, Issue 1-3 https://doi.org/10.1159/000468779	journal	January 1992
MALDI imaging MS of phospholipids in the mouse lung Berry, Karin A. Zemski; Li, Bilan; Reynolds, Susan D. Journal of Lipid Research, Vol. 52, Issue 8 https://doi.org/10.1194/jlr.m015750	journal	April 2011
Design and validation of a histological scoring system for nonalcoholic fatty liver disease Kleiner, David E.; Brunt, Elizabeth M.; Van Natta, Mark Hepatology, Vol. 41, Issue 6 https://doi.org/10.1002/hep.20701	journal	January 2005
A lipidomic analysis of nonalcoholic fatty liver disease Puri, Puneet; Baillie, Rebecca A.; Wiest, Michelle M. Hepatology, Vol. 46, Issue 4 https://doi.org/10.1002/hep.21763	journal	January 2007
Immunolocalization of mitochondrial 3-hydroxy-3-methylgutaryl CoA synthase in rat liver: HMG-CoA SYNTHASE IMMUNOLOCALIZATION Royo, Teresa; Pedragosa, Maria J.; Ayté, José Journal of Cellular Physiology, Vol. 162, Issue 1 https://doi.org/10.1002/jcp.1041620112	journal	January 1995
Liquid Chromatography-Mass Spectrometry (LC-MS)-Based Lipidomics for Studies of Body Fluids and Tissues Nygren, Heli; Seppänen-Laakso, Tuulikki; Castillo, Sandra Methods in Molecular Biology https://doi.org/10.1007/978-1-61737-985-7_15	book	December 2010
Anatomy of the Liver Hoogewoud, Henri-Marcel Hepatocellular Carcinoma and Liver Metastases: Diagnosis and Treatment https://doi.org/10.1007/978-3-642-77981-7_1	book	January 1993
Heterogeneous reciprocal localization of fructose-1,6-bis-phosphatase and of glucokinase in microdissected periportal and perivenous rat liver tissue Katz, Norbert; Teutsch, Harald F.; Jungermann, Kurt FEBS Letters, Vol. 83, Issue 2 https://doi.org/10.1016/0014-5793(77)81021-1	journal	November 1977
Anatomy of the Liver Elias, Hans The Liver https://doi.org/10.1016/B978-1-4832-2824-2.50008-X	book	January 1963
Phosphatidylethanolamine N-methyltransferase from liver Vance, Dennis E.; Walkey, Christopher J.; Cui, Zheng Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, Vol. 1348, Issue 1-2 https://doi.org/10.1016/S0005-2760(97)00108-2	journal	September 1997
Increased hepatocyte CYP2E1 expression in a rat nutritional model of hepatic steatosis with inflammation Weltman, Md; Farrell, Gc; Liddle, C. Gastroenterology, Vol. 111, Issue 6 https://doi.org/10.1016/S0016-5085(96)70028-8	journal	December 1996
The active synthesis of phosphatidylcholine is required for very low density lipoprotein secretion from rat hepatocytes. Yao, Z. M.; Vance, D. E. Journal of Biological Chemistry, Vol. 263, Issue 6 https://doi.org/10.1016/S0021-9258(18)69166-5	journal	February 1988
Kinetic analyses of liver phosphatidylcholine and phosphatidylethanolamine biosynthesis using 13C NMR spectroscopy Reo, N. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, Vol. 1580, Issue 2-3 https://doi.org/10.1016/S1388-1981(01)00202-5	journal	February 2002
Anatomy of the Liver McCuskey, Robert S. Zakim and Boyer's Hepatology https://doi.org/10.1016/b978-1-4160-3258-8.50006-1	book	January 2006
Anatomy of the Liver McCuskey, Robert Zakim and Boyer's Hepatology https://doi.org/10.1016/b978-1-4377-0881-3.00001-2	book	January 2012
Design and Validation of a Histological Scoring System for Nonalcoholic Fatty Liver Disease Bejarano, P. A. Yearbook of Pathology and Laboratory Medicine, Vol. 2006 https://doi.org/10.1016/s1077-9108(08)70034-3	journal	January 2006
In Situ Lipidomic Analysis of Nonalcoholic Fatty Liver by Cluster TOF-SIMS Imaging Debois, Delphine; Bralet, Marie-Pierre; Le Naour, François Analytical Chemistry, Vol. 81, Issue 8 https://doi.org/10.1021/ac900045m	journal	April 2009
Comprehensive LC–MS ^E Lipidomic Analysis using a Shotgun Approach and Its Application to Biomarker Detection and Identification in Osteoarthritis Patients Castro-Perez, Jose M.; Kamphorst, Jurre; DeGroot, Jeroen Journal of Proteome Research, Vol. 10, Issue 7 https://doi.org/10.1021/pr200420k	journal	May 2011
Net Synthesis of Lecithin in an Isolated Enzyme System Weiss, Samuel B.; Smith, Sylvia Wagner; Kennedy, Eugene P. Nature, Vol. 178, Issue 4533 https://doi.org/10.1038/178594a0	journal	September 1956
Increase in long-chain polyunsaturated fatty acid n−6/n−3 ratio in relation to hepatic steatosis in patients with non-alcoholic fatty liver disease Araya, Julia; Rodrigo, Ramón; Videla, Luis A. Clinical Science, Vol. 106, Issue 6 https://doi.org/10.1042/CS20030326	journal	June 2004
Frequency and Outcomes of Liver Transplantation for Nonalcoholic Steatohepatitis in the United States Charlton, Michael R.; Burns, Justin M.; Pedersen, Rachel A. Gastroenterology, Vol. 141, Issue 4 https://doi.org/10.1053/j.gastro.2011.06.061	journal	October 2011
Effect of Anaplerotic Fluxes and Amino Acid Availability on Hepatic Lipoapoptosis Noguchi, Yasushi; Young, Jamey D.; Aleman, Jose O. Journal of Biological Chemistry, Vol. 284, Issue 48 https://doi.org/10.1074/jbc.M109.049478	journal	November 2009
The Membrane Lipid Phosphatidylcholine Is an Unexpected Source of Triacylglycerol in the Liver van der Veen, Jelske N.; Lingrell, Susanne; Vance, Dennis E. Journal of Biological Chemistry, Vol. 287, Issue 28 https://doi.org/10.1074/jbc.M112.381723	journal	July 2012
Targeted Deletion of Hepatic CTP:phosphocholine Cytidylyltransferase α in Mice Decreases Plasma High Density and Very Low Density Lipoproteins Jacobs, René L.; Devlin, Cecilia; Tabas, Ira Journal of Biological Chemistry, Vol. 279, Issue 45 https://doi.org/10.1074/jbc.M404027200	journal	November 2004
Hepatic CTP:Phosphocholine Cytidylyltransferase-α Is a Critical Predictor of Plasma High Density Lipoprotein and Very Low Density Lipoprotein Jacobs, René L.; Lingrell, Susanne; Zhao, Yang Journal of Biological Chemistry, Vol. 283, Issue 4 https://doi.org/10.1074/jbc.M706628200	journal	January 2008
Feature extraction and quantification for mass spectrometry in biomedical applications using the mean spectrum Morris, J. S.; Coombes, K. R.; Koomen, J. Bioinformatics, Vol. 21, Issue 9 https://doi.org/10.1093/bioinformatics/bti254	journal	January 2005
MALDI imaging MS of phospholipids in the mouse lung Berry, Karin A. Zemski; Li, Bilan; Reynolds, Susan D. Journal of Lipid Research, Vol. 52, Issue 8 https://doi.org/10.1194/jlr.M015750	journal	April 2011
Increased Diacylglycerols Characterize Hepatic Lipid Changes in Progression of Human Nonalcoholic Fatty Liver Disease; Comparison to a Murine Model Gorden, D. Lee; Ivanova, Pavlina T.; Myers, David S. PLoS ONE, Vol. 6, Issue 8 https://doi.org/10.1371/journal.pone.0022775	journal	August 2011
Autoregulatory Shift from Fructolysis to Lactate Gluconeogenesis in Rat Hepatocyte Suspensions. The Problem of Metabolic Zonation of Liver Parenchyma Katz, Norbert; Jungermann, Kurt Hoppe-Seyler´s Zeitschrift für physiologische Chemie, Vol. 357, Issue 1 https://doi.org/10.1515/bchm2.1976.357.1.359	journal	January 1976

Cited By (11)

Lipid zonation and phospholipid remodeling in nonalcoholic fatty liver disease: Hall et al. Hall, Zoe; Bond, Nicholas J.; Ashmore, Tom Hepatology, Vol. 65, Issue 4 https://doi.org/10.1002/hep.28953	journal	February 2017
AhR and SHP regulate phosphatidylcholine and S-adenosylmethionine levels in the one-carbon cycle Kim, Young-Chae; Seok, Sunmi; Byun, Sangwon Nature Communications, Vol. 9, Issue 1 https://doi.org/10.1038/s41467-018-03060-y	journal	February 2018
Phospholipid Remodeling in Physiology and Disease Wang, Bo; Tontonoz, Peter Annual Review of Physiology, Vol. 81, Issue 1 https://doi.org/10.1146/annurev-physiol-020518-114444	journal	February 2019
Spatial Systems Lipidomics Reveals Nonalcoholic Fatty Liver Disease Heterogeneity Ščupáková, Klára; Soons, Zita; Ertaylan, Gökhan RWTH Aachen University https://doi.org/10.18154/rwth-conv-237798	text	January 2018
A micro-RNA expression signature for human NAFLD progression Guo, Yan; Xiong, Yanhua; Sheng, Quanghu Journal of Gastroenterology, Vol. 51, Issue 10 https://doi.org/10.1007/s00535-016-1178-0	journal	February 2016
Three-dimensional spatially resolved geometrical and functional models of human liver tissue reveal new aspects of NAFLD progression Segovia-Miranda, Fabián; Morales-Navarrete, Hernán; Kücken, Michael Nature Medicine, Vol. 25, Issue 12 https://doi.org/10.1038/s41591-019-0660-7	journal	December 2019
Total liver phosphatidylcholine content associates with non‐alcoholic steatohepatitis and glycine N‐methyltransferase expression Männistö, Ville; Kaminska, Dorota; Kärjä, Vesa Liver International, Vol. 39, Issue 10 https://doi.org/10.1111/liv.14174	journal	July 2019
Control of oxygen tension recapitulates zone-specific functions in human liver microphysiology systems Lee-Montiel, Felipe T.; George, Subin M.; Gough, Albert H. Experimental Biology and Medicine, Vol. 242, Issue 16 https://doi.org/10.1177/1535370217703978	journal	April 2017
Pre-clinical and clinical investigations of metabolic zonation in liver diseases: The potential of microphysiology systems Soto-Gutierrez, Alejandro; Gough, Albert; Vernetti, Lawrence A. Experimental Biology and Medicine, Vol. 242, Issue 16 https://doi.org/10.1177/1535370217707731	journal	May 2017
Lipid zonation and phospholipid remodeling in nonalcoholic fatty liver disease. Hall, Zoe; Bond, Nicholas J.; Ashmore, Tom Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.7646	text	January 2017
Circulating Phospholipid Patterns in NAFLD Patients Associated with a Combination of Metabolic Risk Factors Tiwari-Heckler, Shilpa; Gan-Schreier, Hongying; Stremmel, Wolfgang Nutrients, Vol. 10, Issue 5 https://doi.org/10.3390/nu10050649	journal	May 2018

Similar Records

Pyruvate dehydrogenase kinase 4 mediates lipogenesis and contributes to the pathogenesis of nonalcoholic steatohepatitis

Journal Article · Sun Jan 14 23:00:00 EST 2018 · Biochemical and Biophysical Research Communications · OSTI ID:23134448

Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

Journal Article · Mon Apr 15 00:00:00 EDT 2013 · Toxicology and Applied Pharmacology · OSTI ID:22285268

Long noncoding RNA lncARSR promotes hepatic lipogenesis via Akt/SREBP-1c pathway and contributes to the pathogenesis of nonalcoholic steatohepatitis

Journal Article · Sun Apr 15 00:00:00 EDT 2018 · Biochemical and Biophysical Research Communications · OSTI ID:23137204

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
fatty liver
histology
lipid metabolism
lipids
nonalcoholic steatohepatitis
obesity
phospholipids
steatosis

Differential Intrahepatic Phospholipid Zonation in Simple Steatosis and Nonalcoholic Steatohepatitis

Citation Formats

References (59)

Cited By (11)

Similar Records

Related Subjects