The measurement, regulation and biological activity of FAHFAs.

Fatty acid esters of hydroxy fatty acids (FAHFAs) are bioactive lipids that are positively correlated with metabolic health in humans and mice. Since their discovery, understanding the role and regulation of FAHFAs has been a prime focus of research into these lipids. In this Review, we describe how FAHFAs are quantitatively measured from biological samples. We then highlight advances in elucidating the genes responsible for the regulation of endogenous FAHFA levels through the degradation, biosynthesis and storage of FAHFAs. We conclude by presenting several examples of antidiabetic and immunomodulatory effects of FAHFAs in cells and in vivo, including their ability to protect against type 1 diabetes. These FAHFA topics are interconnected by their reliance on chemistry and chemical biology to enlighten this frontier of lipid biology, offering new perspectives on metabolic health and potential therapeutic interventions.