BACKGROUND & AIMS: 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.
BACKGROUND & AIMS: 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 obesepatients [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 obesepatients. Thus, FATPs may offer an interesting new approach to understand and potentially intervene NASH pathogenesis.
Authors: Camella G Wilson; Jennifer L Tran; Derek M Erion; Nicholas B Vera; Maria Febbraio; Ethan J Weiss Journal: Endocrinology Date: 2015-12-09 Impact factor: 4.736
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Authors: Lars P Bechmann; Diana Vetter; Junichi Ishida; Rebekka A Hannivoort; Ursula E Lang; Peri Kocabayoglu; M Isabel Fiel; Ursula Muñoz; Gillian L Patman; Fengxia Ge; Shoshana Yakar; Xiaosong Li; Loranne Agius; Young-Min Lee; Weijia Zhang; Kei Yiu Hui; Despina Televantou; Gary J Schwartz; Derek LeRoith; Paul D Berk; Ryozo Nagai; Toru Suzuki; Helen L Reeves; Scott L Friedman Journal: J Hepatol Date: 2013-01-23 Impact factor: 25.083
Authors: M V Machado; G A Michelotti; T de Almeida Pereira; J Boursier; L Kruger; M Swiderska-Syn; G Karaca; G Xie; C D Guy; B Bohinc; K R Lindblom; E Johnson; S Kornbluth; A M Diehl Journal: Gut Date: 2014-07-22 Impact factor: 23.059