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Life sciences · Journal article
Diabetology · September 20, 2026
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Recently, a subset of G protein-coupled receptors (GPCRs) has been deorphanized as nutrient-sensing receptors activated by free fatty acids (FFAs). These GPCRs, termed free fatty acid receptors (FFARs), change their conformation in response to fatty acid binding and transmit extracellular signals into cells to maintain physiological homeostasis. Therefore, FFAs serve a dual role as energy substrates for most body tissues and as signaling molecules. Signaling through FFARs affects various physiological functions, such as metabolic and immune responses. In particular, their role in metabolic regulation has been extensively studied. Thus, FFARs have gained attention as key therapeutic targets for the treatment of obesity and type 2 diabetes. To date, many synthetic agonists for FFARs have been designed and have entered clinical trials, but no agonists have received approval for clinical use. In this review, we summarize and discuss the current knowledge of nutrient signaling mediated by FFARs. We also review the biological importance of FFARs in maintaining metabolic health and recent advances in the translational research of FFAR1 agonists. A better understanding of how FFARs maintain metabolic health may help address global public health problems such as obesity and type 2 diabetes.