Pathophysiology of Nonalcoholic Fatty Liver Disease: Lifestyle-Gut-Gene Interaction
Pathophysiology of Nonalcoholic Fatty Liver Disease: Lifestyle-Gut-Gene Interaction
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DOI：
10.1159/000447275
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发表时间：
2016-01-01
影响因子：
2.3
通讯作者：
Marchesini, Giulio
中科院分区：
文献类型：
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作者：
Mazzotti, Arianna;Caletti, Maria Turchese;Marchesini, Giulio
背景：肝实质脂肪滴的积累是由几个因素驱动的，协同作用增加甘油三酯流向肝脏（饮食和代谢因素，肠道微生物群内毒素血症，遗传因素）。关键信息：在不健康的生活方式和行为因素的存在下，导致脂肪组织扩大和胰岛素抵抗（IR），脂肪分解和新生脂肪生成预计会增加肝脏脂质储存的风险，这与高热量（高脂肪或高碳水化合物）饮食有关。肠道微生物群也可能通过肥胖、IR和由肠道源性毒性因子引起的肝脏炎症参与。最后，一些数据也支持遗传因素的主要作用。一些基因多态性也与非酒精性脂肪性肝病发展和非酒精性脂肪性肝炎进展为更多纤维化和晚期肝病的风险相关。在少数情况下（例如，含patatin样磷脂酶结构域3/脂嘌呤），脂肪变性具有肝脏疾病和心血管发病率/死亡率的高风险；在其他情况下（例如，跨膜6超家族2人类基因），已经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。结论：遗传背景和代谢环境之间的可变相互作用可能是个体病例中涉及的生理病理机制，必须考虑实施有效的治疗策略。(C) 2016 S. Karger AG，巴塞尔
Background: 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). Key Messages: 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. Conclusions: 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. (C) 2016 S. Karger AG, Basel