Interleukin-6 signal transduction and its role in hepatic lipid metabolic disorders

Hepatic lipid dysregulation can lead to spectrum of metabolic disease conditions including metabolic syndrome (MS), fatty liver and diabetes. Liver lipids are regulated by a complex set of extra-hepatic and intra-hepatic factors including cellular cross-talk with variety of cells, inducing various cytokines. Interleukin 6 (IL-6) is a pleiotropic cytokine that exerts both pro-inflammatory and anti-inflammatory effects on hepatic system through either JNK/STAT or ERK/MAPK signaling. Although, IL-6 has shown to protect the liver from fat storage in both rodent and human models and various IL-6(-/-) studies have supported this notion yet a question remains over its deleterious pro-inflammatory effects on hepatocytes. IL-6 ability to produce reactive oxygen species (ROS) and subsequently disturb the hepatic lipid balance has created a conundrum. Furthermore, IL-6 has shown to behave differently under different disease states within hepatocytes and hence, modulating the hepatic lipids accordingly. This review deals with the role of IL-6 on hepatic lipid metabolism and analyzes various data presented on this topic. (c) 2014 Elsevier Ltd. All rights reserved.