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.
In conclusion, despite the fact that the two hepatokines, fetuin-A and fetuin-B, are upregulated in the state of hepatic steatosis in humans, it appears that they differently impact on glucose homeostasis.