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Apoptosis is associated with CD36/fatty acid translocase upregulation in non-alcoholic steatohepatitis
Apoptosis is associated with CD36/fatty acid translocase upregulation in non-alcoholic steatohepatitis
- Source :
- Liver international : official journal of the International Association for the Study of the Liver. 30(6)
- Publication Year :
- 2010
-
Abstract
- 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.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.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.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.
- Subjects :
- Adult
CD36 Antigens
Liver Cirrhosis
Male
Biopsy
Bariatric Surgery
Apoptosis
Fatty Acids, Nonesterified
Middle Aged
Fatty Acid-Binding Proteins
Severity of Illness Index
Body Mass Index
Obesity, Morbid
Up-Regulation
Fatty Liver
Young Adult
Liver
Case-Control Studies
Germany
Humans
Female
RNA, Messenger
Apoptosis Regulatory Proteins
Subjects
Details
- ISSN :
- 14783231
- Volume :
- 30
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Liver international : official journal of the International Association for the Study of the Liver
- Accession number :
- edsair.pmid..........e45fd282d5d3df50d2ffa467b8f4fddc