title: Apoptosis is associated with CD36/fatty acid translocase upregulation in non-alcoholic steatohepatitis.
abstract: OBJECTIVE
  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: x 11.56; FATP-5: x 1.33; CD95/Fas: x 3.18; NOXA: x 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.
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany.
authors.forename: Lars P
authors.initials: LP
authors.lastname: Bechmann
authors.forename: Robert K
authors.initials: RK
authors.lastname: Gieseler
authors.forename: Jan-Peter
authors.initials: JP
authors.lastname: Sowa
authors.forename: Alisan
authors.initials: A
authors.lastname: Kahraman
authors.forename: Jochen
authors.initials: J
authors.lastname: Erhard
authors.forename: Inga
authors.initials: I
authors.lastname: Wedemeyer
authors.forename: Barbara
authors.initials: B
authors.lastname: Emons
authors.forename: Christoph
authors.initials: C
authors.lastname: Jochum
authors.forename: Thorsten
authors.initials: T
authors.lastname: Feldkamp
authors.forename: Guido
authors.initials: G
authors.lastname: Gerken
authors.forename: Ali
authors.initials: A
authors.lastname: Canbay
mesh_terms: D000328:Adult; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000032:analysis / Q000235:genetics; D050110:Bariatric Surgery; D001706:Biopsy; D015992:Body Mass Index; D018955:CD36 Antigens / Q000032:analysis* / Q000235:genetics; D016022:Case-Control Studies; D050556:Fatty Acid-Binding Proteins / Q000032:analysis / Q000235:genetics; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005234:Fatty Liver / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D005260:Female; D005858:Germany; D006801:Humans; D008099:Liver / Q000201:enzymology* / Q000473:pathology*; D008103:Liver Cirrhosis / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000150:complications* / Q000201:enzymology / Q000473:pathology / Q000601:surgery; D012333:RNA, Messenger / Q000032:analysis; D012720:Severity of Illness Index; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D051017:Apoptosis Regulatory Proteins; D018955:CD36 Antigens; D050556:Fatty Acid-Binding Proteins; D005230:Fatty Acids, Nonesterified; D012333:RNA, Messenger