TORC1 modulation in adipose tissue is required for organismal adaptation to hypoxia inDrosophila

ABSTRACT Animals often develop in conditions where environmental conditions such as food, oxygen and temperature fluctuate. The ability to adapt their metabolism to these fluctuations is important to ensure normal development and viability. In most animals, low oxygen (hypoxia) is deleterious, however some animals can alter their physiology to thrive under hypoxia. Here we show that TORC1 modulation in adipose tissue is required for organismal adaptation to hypoxia in Drosophila . We find that hypoxia rapidly suppresses TORC1 kinase signalling in Drosophila larvae via TSC-mediated inhibition of Rheb. We show that this hypoxia-mediated inhibition of TORC1 specifically in the larval fat body is essential for viable development to adulthood. Moreover, we find that these effects of TORC1 inhibition on hypoxia tolerance are mediated through remodeling of fat body lipid droplets and lipid storage. These studies identify the larval adipose tissue as a key hypoxia sensing tissue that coordinates whole-body development and survival to changes in environmental oxygen by modulating TORC1 and lipid storage.