Hepatic fatty acid translocase CD36 upregulation is associated with insulin resistance, hyperinsulinaemia and increased steatosis in non-alcoholic steatohepatitis and chronic hepatitis C

作者：María E. Miquilena-Colina, Elena Lima‐Cabello, Sonia Sánchez‐Campos, María Victoria García‐Mediavilla, Miguel Fernández‐Bermejo, Tamara Lozano-Rodríguez, Javier Vargas‐Castrillón, Xabier Buqué, Begoña Ochoa, Patricia Aspichueta, Javier González‐Gallego, Carmelo García‐Monzón · 发表于：Gut · 年份：2011 · DOI：10.1136/gut.2010.222844 · 被引用次数：453 · 研究领域：Peroxisome Proliferator-Activated Receptors、Liver Disease Diagnosis and Treatment、Cancer, Lipids, and Metabolism

BACKGROUND: Fatty acid translocase CD36 (FAT/CD36) mediates uptake and intracellular transport of long-chain fatty acids in diverse cell types. While the pathogenic role of FAT/CD36 in hepatic steatosis in rodents is well-defined, little is known about its significance in human liver diseases. OBJECTIVE: To examine the expression of FAT/CD36 and its cellular and subcellular distribution within the liver of patients with non-alcoholic fatty liver disease (NAFLD) and chronic hepatitis C virus (HCV) infection. PATIENTS: 34 patients with non-alcoholic steatosis (NAS), 30 with non-alcoholic steatohepatitis (NASH), 66 with HCV genotype 1 (HCV G1) and 32 with non-diseased liver (NL). METHODS: Real-time PCR and western blot analysis were used to assess hepatic FAT/CD36 expression. Computational image analysis of immunostained liver biopsy sections was performed to determine subcellular distribution and FAT/CD36 expression index. RESULTS: Compared with NL, hepatic mRNA and protein levels of FAT/CD36 were significantly higher in patients with NAS (median fold increase 0.84 (range 0.15-1.61) and 0.66 (range 0.33-1.06), respectively); NASH (0.91 (0.22-1.81) and 0.81 (0.38-0.92), respectively); HCV G1 without steatosis (0.30 (0.17-1.59) and 0.33 (0.29-0.52), respectively); and HCV G1 with steatosis (0.85 (0.15-1.98) and 0.87 (0.52-1.26), respectively). In contrast to NL, FAT/CD36 was predominantly located at the plasma membrane of hepatocytes in patients with NAFLD and HCV G1 with steatos...