Adipose mitochondrial metabolism controls body growth by modulating cytokine and insulin signaling

Abstract

Animals need to adapt their growth to fluctuations in nutrient availability to ensure proper development and survival. These adaptations often rely on specific nutrient-sensing tissues and their control of whole-body physiology through inter-organ communication. While the signaling mechanisms that underlie this communication are well studied, the contributions of metabolic alterations in the nutrient-sensing tissues are less clear. Here, we show how reprogramming of adipose mitochondrial metabolism controls whole-body growth in Drosophila larvae. We find that dietary nutrients alter fat body mitochondrial morphology to lower their bioenergetic activity, which we see can rewire fat body glucose metabolism. Strikingly, we find that genetic reduction of mitochondrial bioenergetics just in the fat body is sufficient to accelerate body growth and development. These growth effects are caused by inhibition of the fat-derived adipokine, TNF/Eiger, which leads to enhanced systemic insulin signaling, the main hormonal stimulator of body growth. Our work reveals how reprogramming of mitochondrial metabolism in one nutrient-sensing tissue is able to couple whole body growth to nutrient availability.