Myo-inositol is a key regulator of avian metabolism: From mechanisms to seasonal behavior.

Being naturally hyperglycemic and insulin insensitive, birds maintain plasma glucose levels twice as high as mammals of similar size. Recent evidence suggests that perturbation of myo-inositol (MI) plays a role in mammalian hyperglycemic regulation. Using an integrative approach, we identify a fundamental role of MI in avian metabolism. We show that MI transporters are highly conserved across birds and that dietary MI reduces fat accumulation in Anna's hummingbirds. MI consumption by hummingbirds varies with seasonal changes in body mass, consistent with a regulatory role. Furthermore, MI enhances fatty acid oxidation in avian cells, via effects on pyruvate-dehydrogenase complexes, indicating a role in mitochondrial fuel selection. Our findings underscore the importance of MI in avian metabolism, offering insights into their evolutionary adaptations in the context of insulin insensitivity.