Inosine: novel activator of brown adipose tissue and energy homeostasis

Extracellular purinergic molecules act as signaling molecules that bind to cellular receptors and regulate signaling pathways. Growing evidence suggests that purines regulate adipocyte function and whole-body metabolism. Here, we focus on one specific purine: inosine. Brown adipocytes, which are important regulators of whole-body energy expenditure (EE), release inosine when they are stressed or become apoptotic. Unexpectedly, inosine activates EE in neighboring brown adipocytes and enhances differentiation of brown preadipocytes. Increasing extracellular inosine, either directly by increasing inosine intake or indirectly via pharmacological inhibition of cellular inosine transporters, increases whole-body EE and counteracts obesity. Thus, inosine and other closely related purines might be a novel approach to tackle obesity and associated metabolic disorders by enhancing EE.