Expression and role of forkhead boxcontaining protein O subfamily1 in patients with nonalcoholic fatty liver disease FREE

Abstract:

Objective To study  the expression  of  forkhead  boxcontaining protein O subfamily1 (FOXO1) in patients with nonalcoholic fatty liver disease （NAFLD） and relationship with expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose6phosphatase catalytic subunit（G6PC）， and to evaluate the effect of FOXO1 on the pathogenesis of  NAFLD. Methods NAFLD patients were confirmed by clinical and pathological methods. Localization of  FOXO1 was observed by  immunocytochemistry；FOXO1, PEPCK and G6PC mRNA levels were observed  by RTPCR.
Results The homeostasis model assessment of insulin resistance (HOMAIR) were higher in nonalcoholic steatohepatitis (NASH ) and simple steatosis (SS) group compared with control group （P＜0.001);alanine transaminase (ALT) was higher in NASH group compared with SS and control group（both P＜0.001,or P<0.05), but  there  was  no  significant difference  between SS and control group (P>0.05); With the progress of disease, there were a gradual increase of percentage of  hepatocytes with FOXO1 and mRNA levels of  FOXO1, PEPCK and G6PC in three  groups, there was significant difference between each group (P<0.001). FOXO1 mRNA levels were positive correlated with  HOMAIR, the degree of steatosis and necroinflammatory activity, the expression of both PEPCK mRNA  and G6PC mRNA.
 Conclusion NAFLD patients with normal ALT should also undergo liver biopsy. Expression and activity of FOXO1 are increased in hepatocytes in NASH. FOXO1 mediates the effect of insulin on the gluconeogenic genes PEPCK and G6PC. Steatosis and inflammation are involved in FOXO1 regulation.

［Key words］fatty liver; nonalcoholic fatty liver disease; forkhead  boxcontaining protein O subfamily1; insulin resistance
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［Chin Infect Control，2010，9（2）：81-84