Apoptosis is associated with CD36/fatty acid translocase upregulation in non-alcoholic steatohepatitis.
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.
Bechmann
Lars P
LP
Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany.
Gieseler
Robert K
RK
Sowa
Jan-Peter
JP
Kahraman
Alisan
A
Erhard
Jochen
J
Wedemeyer
Inga
I
Emons
Barbara
B
Jochum
Christoph
C
Feldkamp
Thorsten
T
Gerken
Guido
G
Canbay
Ali
A
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
D051017:Apoptosis Regulatory Proteins; D018955:CD36 Antigens; D050556:Fatty Acid-Binding Proteins; D005230:Fatty Acids, Nonesterified; D012333:RNA, Messenger