Mazzotti Arianna, Caletti Maria Turchese, Sasdelli Anna Simona, Brodosi Lucia, Marchesini Giulio
Unit of Metabolic Diseases and Clinical Dietetics, 'Alma Mater' University, Bologna, Italy.
Dig Dis. 2016;34 Suppl 1:3-10. doi: 10.1159/000447275. Epub 2016 Aug 22.
The accumulation of fat droplets in the hepatic parenchyma is driven by several factors, synergistically acting to increase triglyceride flow to the liver (diet and metabolic factors, endotoxemia from gut microbiota, genetic factors).
In the presence of unhealthy lifestyles and behavioral factors, leading to enlarged adipose tissue and insulin resistance (IR), both lipolysis and de novo lipogenesis are expected to increase the risk of hepatic lipid depots, in association with high calorie (either high-fat or high-carbohydrate) diets. The gut microbiota may also be involved via obesity, IR and hepatic inflammation generated by gut-derived toxic factors. Finally, several data also support a primary role of genetic factors. A few gene polymorphisms have also been associated with the risk of nonalcoholic fatty liver disease development and nonalcoholic steatohepatitis progression to more fibrosis and advanced liver disease. In a few cases (e.g., patatin-like phospholipase domain-containing 3/adiponutrin), steatosis carries a high risk of both liver disease and cardiovascular morbidity/mortality; in other cases (e.g., transmembrane 6 superfamily 2 human gene), dissociation has been observed between the increased risk of liver disease versus cardiovascular disease.
A variable interplay between the genetic background and the metabolic milieu is the likely physiopathologic mechanism involved in individual cases, which must be considered for implementing effective treatment strategies.
肝实质中脂肪滴的积累由多种因素驱动，这些因素协同作用以增加肝脏的甘油三酯流入量（饮食和代谢因素、肠道微生物群引起的内毒素血症、遗传因素）。
在不健康的生活方式和行为因素存在的情况下，会导致脂肪组织增大和胰岛素抵抗（IR），与高热量（高脂肪或高碳水化合物）饮食相关，脂肪分解和从头脂肪生成均可能增加肝脏脂质蓄积的风险。肠道微生物群也可能通过肥胖、IR以及肠道衍生毒性因子产生的肝脏炎症参与其中。最后，一些数据也支持遗传因素起主要作用。一些基因多态性也与非酒精性脂肪性肝病发生风险以及非酒精性脂肪性肝炎进展为更多纤维化和晚期肝病有关。在少数情况下（例如，含patatin样磷脂酶结构域3/脂肪营养蛋白），脂肪变性会带来肝脏疾病和心血管疾病发病/死亡的高风险；在其他情况下（例如，跨膜6超家族2人类基因），已观察到肝脏疾病风险增加与心血管疾病风险增加之间的分离现象。
遗传背景与代谢环境之间的可变相互作用可能是个别病例中涉及的病理生理机制，在实施有效的治疗策略时必须予以考虑。
