Hepatic steatosis is an underlying feature of nonalcoholic fatty liver disease (NAFLD), which is the most common form of liver disease and is present in up to ∼70% of individuals who are overweight. NAFLD is also associated with hypertriglyceridaemia and low levels of HDL, glucose intolerance, insulin resistance and type 2 diabetes mellitus. Hepatic steatosis is a strong predictor of the development of insulin resistance and often precedes the onset of other known mediators of insulin resistance. This sequence of events suggests that hepatic steatosis has a causal role in the development of insulin resistance in other tissues, such as skeletal muscle. Hepatokines are proteins that are secreted by hepatocytes, and many hepatokines have been linked to the induction of metabolic dysfunction, including fetuin A, fetuin B, retinol-binding protein 4 (RBP4) and selenoprotein P. In this Review, we describe the factors that influence the development of hepatic steatosis, provide evidence of strong links between hepatic steatosis and insulin resistance in non-hepatic tissues, and discuss recent advances in our understanding of how steatosis alters hepatokine secretion to influence metabolic phenotypes through inter-organ communication.

肝脂肪变性是非酒精性脂肪性肝病（NAFLD），这是肝脏疾病的最常见形式，并且以最多的底层功能〜70％的人超重。NAFLD还与高甘油三酸酯血症和低水平的HDL，葡萄糖耐量，胰岛素抵抗和2型糖尿病有关。肝脂肪变性是胰岛素抵抗发展的一​​个强有力的预测指标，通常早于其他已知的胰岛素抵抗介质的发作。这一系列事件表明，肝脂肪变性在其他组织（例如骨骼肌）胰岛素抵抗的发展中具有因果作用。肝因子是肝细胞分泌的蛋白质，许多肝因子与代谢功能障碍的诱导有关，包括胎球蛋白A，胎球蛋白B，视黄醇结合蛋白4（RBP4）和硒蛋白P。影响肝脂肪变性的发展，