title: Association of obestatin, ghrelin, and inflammatory cytokines in obese patients with non-alcoholic fatty liver disease.
abstract: BACKGROUND
  Three protein products of ghrelin gene (acylated ghrelin, des-acylated ghrelin, and obestatin) are involved in appetite stimulation and suppression. Additionally, there is some evidence suggesting their involvement in metabolic and inflammatory pathways which may be implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). The aim of this study was to examine the relationships of ghrelin gene products in patients with NAFLD.
  
  
  METHODS
  We included 75 morbidly obese patients with biopsy-proven NAFLD (41 with histologic non-alcoholic steatohepatitis (NASH)) with clinical and laboratory data as well as frozen serum samples from the time of liver biopsy. Fasting serum was assayed for obestatin as well as acylated and des-acyl-ghrelin concentrations using ELISA. Bio-Plex inflammatory cytokine assays were used to profile expression of 17 inflammatory mediators, including IL-6, IL-7, IL-8, G-CSF, CCL2, and MIP-1β.
  
  
  RESULTS
  Patients with NASH had twofold higher concentration of des-acyl-ghrelin than patients with non-NASH (2.58 vs. 1.24 pg/ml, P < 0.02). Ghrelin concentrations in NASH patients with fibrosis stage ≥2 were almost double the concentration of NASH patients with fibrosis stage <2 (8.73 vs. 4.22 pg/ml, P < 0.04). Obestatin levels also increased with the fibrosis stage (2.54 vs. 3.46 pg/ml, P < 0.03). NAFLD patients with higher fibrosis stage had lower IL-7 concentrations (16.89 vs. 10.68 pg/ml, P = 0.014). Obestatin levels at baseline significantly correlated with rate of weight loss after bariatric surgery at various time points.
  
  
  CONCLUSIONS
  This study suggests that products of the GHRL gene may be important for the pathogenesis of NASH and fibrosis. Additional confirmatory studies are needed.
authors: Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA 22042, USA.
authors: Michael
authors: M
authors: Estep
authors: Massih
authors: M
authors: Abawi
authors: Mohammed
authors: M
authors: Jarrar
authors: Lei
authors: L
authors: Wang
authors: Maria
authors: M
authors: Stepanova
authors: Hazem
authors: H
authors: Elariny
authors: Amir
authors: A
authors: Moazez
authors: Zachary
authors: Z
authors: Goodman
authors: Vikas
authors: V
authors: Chandhoke
authors: Ancha
authors: A
authors: Baranova
authors: Zobair M
authors: ZM
authors: Younossi
mesh_terms: D016207:Cytokines / Q000097:blood*; D005234:Fatty Liver / Q000097:blood* / Q000150:complications*; D005260:Female; D054439:Ghrelin / Q000097:blood*; D006801:Humans; D007249:Inflammation / Q000209:etiology; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D009767:Obesity, Morbid / Q000097:blood* / Q000150:complications*
chemical_list: D016207:Cytokines; D054439:Ghrelin