Targeting sweet taste receptor T1R2/T1R3: a new strategy for metabolic disease regulation and intervention of multiple organ diseases

The overconsumption of dietary sugars poses significant health risks, creating a conflict with the innate human preference for sweet taste. Beyond its role in taste perception on the tongue, the sweet taste receptor (STR, a heterodimer of T1R2/T1R3) serves as a crucial nutrient sensor in metabolic organs, including the gut and pancreas. Dysfunction of this receptor is linked to impaired metabolic regulation. This review comprehensively summarizes the structure and signaling pathways of T1R2/T1R3, with a particular focus on its interaction with various food-source sweet ligands, including natural sugars and sweeteners. We further discuss its implications in metabolic diseases and its role beyond taste in systems such as the immune system. Finally, we highlight the receptor's significant potential in food innovation, encompassing the development of novel sweeteners, tailored dietary strategies, and biosensors for food quality and safety, offering new avenues for managing health through diet. • Prospects for creating functional foods that target T1R2/T1R3 are provided. • The challenges of food-based intervention targeting T1R2/T1R3 are discussed. • The great potential of this receptor in food and drug innovation is emphasized.