A fat-tissue sensor couples growth to oxygen availability by remotely controlling insulin secretion

Abstract

Organisms adapt their metabolism and growth to the availability of nutrients and oxygen, which are essential for normal development. This requires the ability to sense these environmental factors and respond by regulation of growth-controlling signals, yet the mechanisms by which this adaptation occurs are not fully understood. To identify novel growth-regulatory mechanisms, we conducted a global RNAi-based screen in Drosophila for size differences and identified 89 positive and negative regulators of growth. Among the strongest hits was the FGFR homologue breathless necessary for proper development of the tracheal airway system. Breathless deficiency results in tissue hypoxia (low oxygen), sensed primarily in this context by the fat tissue. The fat, in response, relays this information through release of one or more humoral factors that remotely inhibit insulin secretion from the brain, thereby restricting systemic growth. Thus our findings show that the fat tissue acts as an oxygen sensor that allows the organism to reduce its growth in adaptation to limited oxygen conditions.