Division of Gastro-Hepatology, San Giovanni Battista Hospital, University of Turin, C. so Bramante 88, 10126 Turin, Italy.
Dig Liver Dis. 2010 May;42(5):320-30. doi: 10.1016/j.dld.2010.01.016. Epub 2010 Mar 6.
The metabolic syndrome encompasses metabolic and cardiovascular risk factors which predict diabetes and cardiovascular disease (CVD) better than any of its individual components. Nonalcoholic fatty liver disease (NAFLD) comprises a disease spectrum which includes variable degrees of simple steatosis (nonalcoholic fatty liver, NAFL), nonalcoholic steatohepatitis (NASH) and cirrhosis. NAFLD is the hepatic manifestation of the metabolic syndrome, with insulin resistance as the main pathogenetic mechanism. Recent data indicate that hyperinsulinemia is probably the consequence rather than cause of NAFLD and NAFLD can be considered an independent predictor of cardiovascular disease. Serum free fatty acids derived from lipolysis of visceral adipose tissue are the main source of hepatic triglycerides in NAFLD, although hepatic de novo lipogenesis and dietary fat supply contribute to the pathogenesis of NAFLD. Approximately 10-25% NAFLD patients develop NASH, the evolutive form of hepatic steatosis. Presumably in a genetically predisposed environment, this increased lipid overload overwhelms the oxidative capacity and reactive oxygen species are generated, leading to lipid peroxidation, cytokine induction, chemoattraction of inflammatory cells, hepatic stellate cell activation and finally fibrogenesis with extracellular matrix deposition. No currently available therapies for NAFLD and NASH exist. Recently nuclear receptors have emerged as key regulators of lipid and carbohydrate metabolism for which specific pharmacological ligands are available, making them attractive therapeutic targets for NAFLD and NASH.
代谢综合征包括代谢和心血管危险因素，其预测糖尿病和心血管疾病 (CVD) 的能力优于其任何单个成分。非酒精性脂肪性肝病 (NAFLD) 包括一个疾病谱，其中包括不同程度的单纯性脂肪变性 (非酒精性脂肪肝，NAFL)、非酒精性脂肪性肝炎 (NASH) 和肝硬化。NAFLD 是代谢综合征的肝脏表现，胰岛素抵抗是主要的发病机制。最近的数据表明，高胰岛素血症可能是 NAFLD 的后果而不是原因，NAFLD 可以被认为是心血管疾病的独立预测因子。来自内脏脂肪分解的血清游离脂肪酸是 NAFLD 中肝甘油三酯的主要来源，尽管肝从头合成和膳食脂肪供应有助于 NAFLD 的发病机制。大约 10-25%的 NAFLD 患者发展为 NASH，这是肝脂肪变性的进行性形式。推测在遗传易感性的环境中，这种增加的脂质过载会超过氧化能力，产生活性氧物质，导致脂质过氧化、细胞因子诱导、炎症细胞趋化、肝星状细胞激活，最终导致细胞外基质沉积的纤维化。目前尚无针对 NAFLD 和 NASH 的有效治疗方法。最近，核受体已成为脂质和碳水化合物代谢的关键调节剂，针对这些调节剂已经有特定的药理学配体，使它们成为 NAFLD 和 NASH 的有吸引力的治疗靶点。
