Apoptosis is associated with CD36/fatty acid translocase upregulation in non-alcoholic steatohepatitis
2009; Wiley; Volume: 30; Issue: 6 Linguagem: Inglês
10.1111/j.1478-3231.2010.02248.x
ISSN1478-3231
AutoresLars P. Bechmann, Robert K. Gieseler, Jan‐Peter Sowa, Alişan Kahraman, J. Erhard, Inga Wedemeyer, Barbara Emons, Christoph Jochum, Thorsten Feldkamp, Guido Gerken, Ali Canbay,
Tópico(s)Peroxisome Proliferator-Activated Receptors
ResumoLiver InternationalVolume 30, Issue 6 p. 850-859 Apoptosis is associated with CD36/fatty acid translocase upregulation in non-alcoholic steatohepatitis Lars P. Bechmann, Lars P. Bechmann Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, GermanySearch for more papers by this authorRobert K. Gieseler, Robert K. Gieseler Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany Division of R&D, Rodos BioTarget GmbH, Hannover, GermanySearch for more papers by this authorJan-Peter Sowa, Jan-Peter Sowa Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, GermanySearch for more papers by this authorAlisan Kahraman, Alisan Kahraman Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, GermanySearch for more papers by this authorJochen Erhard, Jochen Erhard Department of Surgery, Evangelic Hospital Dinslaken, Dinslaken, GermanySearch for more papers by this authorInga Wedemeyer, Inga Wedemeyer Department of Pathology, University of Cologne, Cologne, GermanySearch for more papers by this authorBarbara Emons, Barbara Emons Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, GermanySearch for more papers by this authorChristoph Jochum, Christoph Jochum Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, GermanySearch for more papers by this authorThorsten Feldkamp, Thorsten Feldkamp Department of Nephrology, University Hospital Essen, Essen, GermanySearch for more papers by this authorGuido Gerken, Guido Gerken Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, GermanySearch for more papers by this authorAli Canbay, Ali Canbay Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, GermanySearch for more papers by this author Lars P. Bechmann, Lars P. Bechmann Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, GermanySearch for more papers by this authorRobert K. Gieseler, Robert K. Gieseler Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany Division of R&D, Rodos BioTarget GmbH, Hannover, GermanySearch for more papers by this authorJan-Peter Sowa, Jan-Peter Sowa Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, GermanySearch for more papers by this authorAlisan Kahraman, Alisan Kahraman Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, GermanySearch for more papers by this authorJochen Erhard, Jochen Erhard Department of Surgery, Evangelic Hospital Dinslaken, Dinslaken, GermanySearch for more papers by this authorInga Wedemeyer, Inga Wedemeyer Department of Pathology, University of Cologne, Cologne, GermanySearch for more papers by this authorBarbara Emons, Barbara Emons Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, GermanySearch for more papers by this authorChristoph Jochum, Christoph Jochum Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, GermanySearch for more papers by this authorThorsten Feldkamp, Thorsten Feldkamp Department of Nephrology, University Hospital Essen, Essen, GermanySearch for more papers by this authorGuido Gerken, Guido Gerken Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, GermanySearch for more papers by this authorAli Canbay, Ali Canbay Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, GermanySearch for more papers by this author First published: 31 May 2010 https://doi.org/10.1111/j.1478-3231.2010.02248.xCitations: 67 Correspondence Ali Canbay, MD, University Hospital Essen, Hufelandstr. 55, 45122 Essen, GermanyTel: +49 201 723 84713Fax:+49 201 723 5712e-mail: ali.canbay@uni-due.de Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Background & aims: Hepatocyte apoptosis is a key event in non-alcoholic steatohepatitis (NASH). We studied the effect of obesity on free fatty acid (FFA) levels, fatty acid transport proteins (FATPs) and on extrinsic and intrinsic activation of apoptosis in the liver. Methods: Liver biopsies were harvested from 52 morbidly obese patients [body mass index (BMI): 53.82±1.41; age: 45±10.50; 15 males/37 females] undergoing bariatric surgery, and were scored for NASH, evaluated for fibrosis, and investigated for intrahepatic expression of FATPs, death receptors and cytosolic apoptosis-related molecules. Findings were correlated with serum FFA levels and the degrees of intrahepatic (terminal dUTP nick end labelling) and systemic (M30) apoptosis. Results: In patients' liver sections, FATPs as well as select parameters of extrinsic and intrinsic apoptosis were found to be upregulated (CD36/FAT: × 11.56; FATP-5: × 1.33; CD95/Fas: × 3.18; NOXA: × 2.79). These findings correlated with significantly elevated serum FFAs (control: 14.72±2.32 mg/dl vs. patients: 23.03±1.24 mg/dl) and M30 levels (control: 83.12±7.46 U/L vs. patients: 212.61±22.16 U/L). We found correlations between FATPs and apoptosis mediators as well as with histological criteria of NASH and fibrosis. Conclusions: Increased FFA and FATPs are associated with extrinsically and intrinsically induced apoptosis, liver damage and fibrosis in obese patients. Thus, FATPs may offer an interesting new approach to understand and potentially intervene NASH pathogenesis. Citing Literature Supporting Information Fig. S1. Select parameters are presented by activation of FoxO3a. Expression of CD36/FAT, FABP and NOXA (as are related to the intrinsic pathway of apoptosis) are clearly elevated in pFoxO3a-low patients. Conversely, the extrinsic apoptosis pathway, as indicated by caspase-8 and FasL expression, is downregulated in pFoxO3a-low patients when compared to patients with high levels of phosphorylated FoxO3a. The same was found for adiponectin with its antiapoptotic, insulin resistance-promoting and regulatory properties. Due to the small sample size, these differences did not reach statistical significance. Please note: Wiley-Blackwell is not responsible for the content or functionality of any supporting materials supplied by the authors. Any queries (other than missing material) should be directed to the corresponding author for the article. Filename Description LIV_2248_sm_supplfig1.jpg342.8 KB Supporting info item Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume30, Issue6July 2010Pages 850-859 RelatedInformation
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