Preclinical insights into the potential of itaconate and its derivatives for liver disease therapy

Annually, approximately 3.5 % of the world's population dies of cirrhosis or liver cancer, and the burden of liver disease is steadily expanding owing to multiple factors such as alcohol consumption, irrational diets, viral transmission, and exposure to drugs and toxins. However, the lack of effective therapies and the adverse effects of some medications remain a threat to the management of liver disease. Recently, immunometabolism, as an emerging discipline, appears to be the focus of unprecedented research. As a natural metabolite that regulates cellular functions, itaconate is a crucial bridge connecting metabolism and immune response. Remodeling immune function through metabolic modulation may be a promising alternative for disease intervention strategies. In this review, we first briefly describe the historical origin of itaconate and the development of its derivatives. This was followed by a review of the molecular mechanisms by which itaconate regulated immune-metabolic responses. Furthermore, we analyzed the effects of itaconate regulation on immune cells of the hepatic system. Finally, we summarized the experimental evidence for itaconate and its derivatives in the therapeutic application of liver diseases. Itaconate is potentially an invaluable component of emerging therapeutic strategies for liver disease.