An essential role for glial cells in postingestive nutrient sensing

Behavioral flexibility is an essential trait for survival of any organism. For example, choosing an appropriate food source is vital. To do so, the food’s nutritive value needs to be evaluated. Several studies have demonstrated that Drosophila melanogaster larvae and adults, as mammals, are able to distinguish between nutritious and non-nutritious carbohydrates independent of their taste. Several groups of neurons have been implicated in postprandial sugar sensing in adult flies (Dus et al., 2011, 2015; Miyamoto et al., 2012; Park et al., 2016; Musso et al., 2023). In larvae, neurons expressing Gr43a, a fructose receptor, have been shown to be implicated in postingestive glucose sensing (Mishra et al., 2013). How can a fructose sensor mediate glucose sensing? We show that postingestive glucose, and also sorbitol, sensing involves carbohydrate conversion into fructose via the polyol pathway in glial cells. Glia-derived fructose is subsequently sensed via Gr43a expressed in neurons, which leads to behavioral adaptation. Thus, in postingestive nutrient sensing, the glial cells play a central role in information processing and regulation of behavior.