Notch signaling in metabolic diseases: A key regulator and potential target

The incidence of metabolic diseases, particularly obesity, has been rising annually, exerting a profound influence on global health, the economy, and society. Consequently, there is an urgent need to elucidate the pathogenesis of these diseases and develop effective therapeutic strategies. The Notch signaling pathway is an evolutionarily conserved cell signaling that mediates cell-to-cell communication. It is well known for its regulatory role in cell fate determination, tissue development, and organogenesis. Emerging evidence indicates that aberrant activation of Notch signaling pathway can impair energy homeostasis and cause metabolic disorders, promoting the progression of obesity, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), diabetes, and cardiovascular diseases. This review comprehensively summarizes the mechanisms underlying the pathophysiological functions of the Notch signaling pathway in metabolic diseases, including obesity, NAFLD, NASH, diabetes, and atherosclerosis. Furthermore, Notch inhibition therapies are introduced to identify potential therapeutic targets for metabolic diseases.