title: Fetuin-A mRNA expression is elevated in NASH compared with NAFL patients.
abstract: Fetuin-A is a pro-inflammatory protein expressed by hepatocytes. Its course in morbidly obese patients with NAFLD (non-alcoholic fatty liver disease) following weight loss by BAS (bariatric surgery) has not been fully elucidated yet. In the present study, we prospectively examined the effects of weight loss on various metabolic factors at 4 weeks and 6 months after surgery. Blood and liver tissues were retrieved from 108 morbidly obese NAFLD patients before/during BAS, and 50 of these individuals met the criteria for NASH (non-alcoholic steatohepatitis). Fetuin-A expression was measured by qPCR (quantitative real-time PCR), Western blotting and immunohistochemistry. Hepatocyte apoptosis was quantified via M30 (caspase-cleaved cytokeratin-18 fragments). Plasma concentrations of adiponectin and fetuin-A were determined by ELISA. Serum-derived parameters were additionally taken at 4 weeks and 6 months post-operatively. In addition, primary human hepatocytes were treated with NEFA (non-esterified fatty acid) to investigate changes in fetuin-A. BMI (body mass index) decreased significantly from 53.0±1.1 to 36.4±1.9 kg/m2 in the NAFL group and from 53.3±1.1 to 37.6±1.2 kg/m2 in the NASH group (P<0.0001) at 6 months post-surgery. This was associated with diminishing M30 and M65 (total cytokeratin-18) levels over 6 months after surgery. Adiponectin levels increased continuously in NASH patients, whereas NAFL patients plateaued at 4 weeks post-operatively. Hepatic fetuin-A mRNA and protein expression was elevated before surgery-induced weight loss. However, plasma concentrations of fetuin-A increased signficantly in NASH patients 4 weeks post-operatively. Treatment of hepatocytes with NEFA led to up-regulation of fetuin-A expression. BAS probably has a beneficial effect on NAFLD, as indicated by reduced hepatocyte apoptosis and improved adipokine profiles. In addition, fetuin-A expression is more prominent in NASH.
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: Alisan
authors.initials: A
authors.lastname: Kahraman
authors.forename: Jan-Peter
authors.initials: JP
authors.lastname: Sowa
authors.forename: Martin
authors.initials: M
authors.lastname: Schlattjan
authors.forename: Svenja
authors.initials: S
authors.lastname: Sydor
authors.forename: Martin
authors.initials: M
authors.lastname: Pronadl
authors.forename: Alexander
authors.initials: A
authors.lastname: Wree
authors.forename: Anja
authors.initials: A
authors.lastname: Beilfuss
authors.forename: Alpaslan
authors.initials: A
authors.lastname: Kilicarslan
authors.forename: Akif
authors.initials: A
authors.lastname: Altinbaş
authors.forename: Lars Peter
authors.initials: LP
authors.lastname: Bechmann
authors.forename: Wing-Kin
authors.initials: WK
authors.lastname: Syn
authors.forename: Guido
authors.initials: G
authors.lastname: Gerken
authors.forename: Ali
authors.initials: A
authors.lastname: Canbay
mesh_terms: D052242:Adiponectin / Q000097:blood; D000328:Adult; D017209:Apoptosis; D050110:Bariatric Surgery; D015153:Blotting, Western; D015992:Body Mass Index; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology; D005234:Fatty Liver / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D053538:Keratin-18 / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease; D009767:Obesity, Morbid / Q000235:genetics / Q000378:metabolism / Q000601:surgery; D010446:Peptide Fragments / Q000378:metabolism; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D060749:alpha-2-HS-Glycoprotein / Q000235:genetics* / Q000378:metabolism
chemical_list: D052242:Adiponectin; D005230:Fatty Acids, Nonesterified; D053538:Keratin-18; C561463:M30 cytokeratin-18 peptide, human; C577325:M65 antigen, human; D010446:Peptide Fragments; D012333:RNA, Messenger; D060749:alpha-2-HS-Glycoprotein