Caldwell Stephen H, Ikura Yoshihiro, Iezzoni Julia C, Liu Zhenqi
Division of GI/Hepatology, Digestive Health Center of Excellence, University of Virginia, Charlottesville, Virginia 22908-0708, USA.
J Gastroenterol Hepatol. 2007 Jun;22 Suppl 1:S11-9. doi: 10.1111/j.1440-1746.2006.04639.x.
Fatty liver is closely related to the development of the insulin resistance syndrome that largely results from abnormal insulin signaling in three major organs: (i) skeletal muscle in which insulin sensitivity depends on fat content and metabolic activity (exercise); (ii) adipose tissue, which serves as a reservoir of energy in the form of triglycerides; and (iii) the liver, which variably serves as a source or storage site of carbohydrates and lipids. In many respects, the fatty liver resembles a mixture of brown adipose tissue (microvesicular steatosis) and white adipose tissue (macrovesicular steatosis) including the stages of fatty droplet accumulation, and the expression of uncoupling proteins and perilipin-like substances. Furthermore, the development of an inflammatory infiltrate and the increased production of cytokines as occurs in adipose tissue, suggest that the liver in some individuals serves as an extension of adipose tissue. Moreover, current evidence indicates that these morphological changes represent altered gene expression similar to that of adipocytes. However, fatty liver does not appear to be a uniform feature of the metabolic syndrome and there is substantial variation in humans in the development of fatty liver independent of insulin resistance. In this regard, the variable development of fatty liver in Palmipedes (migratory fowl) and its close relationship to skeletal muscle utilization of fatty acids, lipoprotein metabolism and thermoregulation are instructive. The predilection to non-alcoholic fatty liver disease among some varieties of Palmipedes suggests that the development of fatty liver represents an adaptive process, closely integrated with skeletal muscle fat utilization and adipose tissue distribution, and facilitates survival in a very cold, resource-scarce environment. Variation in human populations with metabolic syndrome likewise suggests that the trait evolved in populations exposed in ancient times to different environmental challenges and, because the liver plays a central role in lipid metabolism, the presence or absence of fatty liver is likely to be integrated with insulin sensitivity in other target organs and with lipoprotein metabolism.
脂肪肝与胰岛素抵抗综合征的发生密切相关，而胰岛素抵抗综合征主要源于三个主要器官中胰岛素信号的异常：（i）骨骼肌，其中胰岛素敏感性取决于脂肪含量和代谢活性（运动）；（ii）脂肪组织，它作为甘油三酯形式的能量储存库；（iii）肝脏，它可变地作为碳水化合物和脂质的来源或储存部位。在许多方面，脂肪肝类似于棕色脂肪组织（微泡性脂肪变性）和白色脂肪组织（大泡性脂肪变性）的混合物，包括脂肪滴积累阶段、解偶联蛋白和类脂联素物质的表达。此外，炎症浸润的发展以及细胞因子产生的增加，如同在脂肪组织中发生的那样，表明在某些个体中肝脏充当了脂肪组织的延伸。而且，目前的证据表明这些形态学变化代表了与脂肪细胞类似的基因表达改变。然而，脂肪肝似乎并不是代谢综合征的一个统一特征，并且在人类中，脂肪肝的发生存在很大差异，与胰岛素抵抗无关。在这方面，水鸟（候鸟）中脂肪肝的可变发展及其与骨骼肌脂肪酸利用、脂蛋白代谢和体温调节的密切关系具有启发性。某些水鸟品种中对非酒精性脂肪肝病的易感性表明，脂肪肝的发生代表了一个适应性过程，与骨骼肌脂肪利用和脂肪组织分布紧密结合，并有助于在非常寒冷、资源稀缺的环境中生存。患有代谢综合征的人群中的差异同样表明，该特征在古代面临不同环境挑战的人群中进化而来，并且由于肝脏在脂质代谢中起核心作用，脂肪肝的存在与否可能与其他靶器官的胰岛素敏感性以及脂蛋白代谢相关联。
