These authors equally contributed to this work.
Steatohepatitis/Metabolic Liver Disease
Article first published online: 8 APR 2013
Copyright © 2013 American Association for the Study of Liver Diseases
Volume 57, Issue 4, pages 1394–1406, April 2013
How to Cite
Bechmann, L. P., Kocabayoglu, P., Sowa, J.-P., Sydor, S., Best, J., Schlattjan, M., Beilfuss, A., Schmitt, J., Hannivoort, R. A., Kilicarslan, A., Rust, C., Berr, F., Tschopp, O., Gerken, G., Friedman, S. L., Geier, A. and Canbay, A. (2013), Free fatty acids repress small heterodimer partner (SHP) activation and adiponectin counteracts bile acid-induced liver injury in superobese patients with nonalcoholic steatohepatitis. Hepatology, 57: 1394–1406. doi: 10.1002/hep.26225
Potential conflict of interest: Dr. Rust is on the speakers' bureau for Falk Foundation.
Supported by the Deutsche Forschungsgemeinschaft (DFG, grant 267/4-1 and 267/8-1; to A.C.), Swiss National Foundation (grant 310000-122310/1; to A.G.), the Wilhelm Laupitz Foundation (to A.C.), EASL Sheila Sherlock short-term fellowship (to L.P.B.), IFORES program of the University of Duisburg-Essen (to L.P.B.).
- Issue published online: 8 APR 2013
- Article first published online: 8 APR 2013
- Accepted manuscript online: 8 JAN 2013 07:14PM EST
- Manuscript Accepted: 5 NOV 2012
- Manuscript Received: 13 MAR 2012
- Deutsche Forschungsgemeinschaft. Grant Numbers: 267/4-1, 267/8-1
- Swiss National Foundation. Grant Number: 310000-122310/1
- Wilhelm Laupitz Foundation
- EASL Sheila Sherlock short-term fellowship
- IFORES program of the University of Duisburg-Essen
Additional Supporting Information may be found in the online version of this article.
|HEP_26225_sm_SuppFigS1.tif||2039K||Supporting Figure S1: Serum markers of cell death and adiponectin in all patient cohorts. The cell death markers M30 and M65 as well as adiponectin are shown for healthy controls, moderately overweight (“lean”) NAFLD patients and the super-obese NAFLD cohort. All patients exhibited higher cell death compared to healthy controls. Adiponectin was not only significantly reduced in “lean” NAFLD and super-obese NAFLD, but in addition super-obese NAFLD patients had lower adiponectin serum concentrations than “lean” NAFLD.|
|HEP_26225_sm_SuppFigS2.tif||4579K||Supporting Figure S2: (A) The bile acid synthesis intermediate cholestenon and serum cholesterol do not differ between the groups. (B) The amount of cholesterol within the liver tissue did not differ between NAFL and NASH patients.|
|HEP_26225_sm_SuppFigS3.tif||3380K||Supporting Figure S3: In HepG2 cells, treated with FFA, we found a significant induction of Cyp7A1 (A) and NTCP (B), which could be attenuated by CDCA co-treatment, indicating a dysregulation of baseline SHP activity by FFA abundance, similar to the clinical findings. Expression of SHP (C) itself was significantly reduced by adiponectin, FFA or both. Again addition of CDCA abolished this effect. LXRa (D) as well SREBPc1 (E) were not altered on the level of mRNA expression by FFA, adiponectin, CDCA or combinations thereof. Cell viability, analyzed by MTT test (F) was similar in all experimental conditions. * = p ≤ 0.05; ** = p ≤ 0.001; *** = p ≤ 0.0001 vs. Control cells.|
|HEP_26225_sm_SuppFigS4.tif||70K||Supporting Figure S4: Regulatory gene expression. mRNA expression of p21, FASN and SREBP1 was not changed between the “lean” NALFD, NAFL or NASH group.|
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