非酒精性脂肪性肝病的发病机制和动物模型

llular steatosis)(单纯性脂肪肝)Р脂肪性肝炎(nonalcoholic steatohepatitis,NASH)Р肝纤维化(fibrosis)Р肝硬化(cirrhosis)РNAFLD的自然病程Р胰岛素抵抗(Insulin resistance)?糖耐量异常\糖尿病(Glucose intolerance or diabetes)?中心性肥胖(Central obesity)?高血压(Hypertension)?血脂异常(Dyslipidaemia)?肝细胞癌(hepatocellular carcinoma)РNAFLD伴随\相关疾病РThe ‘first hit’Р脂质积累,脂肪变性?(Steatosis)РNAFLD发病机制一:The ‘2-hit hypothesis’РThe key role of free fatty acids (FFA)РNAFLD发病机制一:The ‘2-hit hypothesis’РThe ‘third hit’(a central feature of NAFLD pathogenesis)? inadequate hepatocyte proliferationРNAFLD发病机制一:The ‘2-hit hypothesis’РNAFLD肝脏中FFAs来源:? lipolysis of adipose tissue(60%)? dietary sources(15%)? de novo lipogenesis(25%)?NAFLD肝脏中FFAs的去向:? β-oxidation? triglycerides( lipid droplets)? VLDLРNAFLD发病机制二:Lipid accumulation/steatosisРNAFLD发病机制二:Lipid accumulation/steatosis