Hepatokines: linking nonalcoholic fatty liver disease and insulin resistance

Nonalcoholic fatty liver disease (NAFLD) is present in ∼20–40% of adults in the USA, and in ∼70% and >90% of individuals worldwide with overweight or morbid obesity, respectivelyHepatic lipid content is regulated by the complex interplay between the delivery of lipids to the liver and the processes of hepatic lipid uptake, synthesis, oxidation and secretionHepatic fat content is the strongest predictor of insulin resistance in skeletal muscle, hepatic and adipose tissuesHepatokines are proteins secreted by hepatocytes that can influence metabolic processes through autocrine, paracrine and endocrine signallingHepatic steatosis induces changes in hepatokine secretion that promote insulin resistance and that negatively affect other metabolic processesA better understanding of hepatokine function in hepatic steatosis will inform the prevention, diagnosis and treatment of a range of metabolic diseases, including type 2 diabetes mellitus