A vicious circle between insulin resistance and inflammation in nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) comprises a spectrum of diseases, including simple steatosis, nonalcoholic steatohepatitis (NASH), liver cirrhosis and hepatocellular carcinoma. Lipotoxicity, insulin resistance (IR) and inflammation are involved in the disease process. Lipotoxicity promotes inflammation and IR, which in turn, increase adipocyte lipolysis and exacerbates lipotoxicity. Furthermore, IR and inflammation form a vicious circle, with each condition promoting the other and accelerating the development of NAFLD in the presence of lipotoxicity. As an integrator of inflammatory pathway networks, nuclear factor-kappa B (NF-κB) regulates expression of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and anti-inflammatory cytokines, such as adiponectin in NAFLD. In this review, the relationships between lipotoxicity, IR and inflammation in NAFLD are discussed, with particular emphasis on the inflammatory pathways.