title: Expression of cytokine signaling genes in morbidly obese patients with non-alcoholic steatohepatitis and hepatic fibrosis.
abstract: BACKGROUND
  White adipose tissue (WAT) from visceral adiposity plays an important role in the pathogenesis of non-alcoholic steatohepatitis (NASH). Development of NASH and its progression to fibrosis is partially due to cytokines and adipokines produced by WAT. The aim of this study was to assess the association of hepatic fibrosis and NASH by evaluating the intrinsic differences in the inflammatory cytokine signaling in the visceral adipose tissue obtained from morbidly obese patients.
  
  
  METHODS
  We used targeted microarrays representing human genes involved in the inflammatory and fibrogenic reactions to profile visceral adipose samples of 15 well-matched NASH patients with and without fibrosis. Additionally, visceral adipose samples were subjected to real-time polymerase chain reaction profiling of 84 inflammations related genes.
  
  
  RESULTS
  Eight genes (CCL2, CCL4, CCL18, CCR1, IL10RB, IL15RA, and LTB) were differentially expressed in NASH with fibrosis. Additionally, an overlapping but distinct list of the differentially expressed genes were found in NASH with type II diabetes (DM; IL8, BLR1, IL2RA, CD40LG, IL1RN, IL15RA, and CCL4) as compared to NASH without DM.
  
  
  CONCLUSIONS
  Inflammatory cytokines are differentially expressed in the adipose tissue of NASH with fibrosis, as well in NASH with DM. These findings point at the interaction of adipose inflammatory cytokines, DM, hepatic fibrosis in NASH, and its progression to cirrhosis and end-stage liver disease.
authors.affiliation: Center for Liver Diseases, Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA, 22042, USA.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Estep
authors.forename: Ancha
authors.initials: A
authors.lastname: Baranova
authors.forename: Noreen
authors.initials: N
authors.lastname: Hossain
authors.forename: Hazem
authors.initials: H
authors.lastname: Elariny
authors.forename: Kathy
authors.initials: K
authors.lastname: Ankrah
authors.forename: Arian
authors.initials: A
authors.lastname: Afendy
authors.forename: Vikas
authors.initials: V
authors.lastname: Chandhoke
authors.forename: Zobair M
authors.initials: ZM
authors.lastname: Younossi
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics / Q000473:pathology; D005234:Fatty Liver / Q000150:complications / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D050152:Intra-Abdominal Fat; D008103:Liver Cirrhosis / Q000150:complications / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D018121:Receptors, Cytokine / Q000235:genetics*
chemical_list: D016207:Cytokines; D018121:Receptors, Cytokine