Starvation is a common environmental stress. Survival during starvation requires pervasive transcriptional, metabolic, and physiological changes. The forkhead box transcription factor
daf-16/FoxO is known for its essential role in mounting a starvation response. However, effectors of
daf-16/FoxO are poorly understood. We define a set of genes regulated by
daf-16/FoxO during starvation in C. elegans L1 larvae. We find that
daf-16/FoxO functions early in starvation to transcriptionally control metabolic enzymes, promoting a metabolic shift to utilize the glyoxylate shunt, gluconeogenesis, and synthesize trehalose, a disaccharide of glucose. Defective trehalose synthesis reduces starvation survival, and trehalose supplementation during starvation increases survival. Ablation of the trehalose 6-phosphate synthase enzymes
tps-1 and
tps-2 demonstrates they are required to use other sugars and maintain the steady state pool of trehalose, contributing to survival. RNA-seq analyses reveal that trehalose supplementation does not fully complement elimination of trehalose synthase activity, suggesting a physiological role of the phosphorylated intermediate, trehalose 6-phosphate, or a secondary function of trehalose synthase enzymes. While trehalose is well known for its ability to buffer macromolecules during stress, our results also suggest it functions as an energy source to extend starvation survival. As an energy source, trehalose can fuel cell division in at least two different tissues. These observations and others support the model that trehalose is produced in the intestine during starvation and is used to fuel glycolysis in other tissues. This work reveals an integral role for trehalose in organismal energy homeostasis, and it demonstrates that
daf-16/FoxO promotes starvation survival by modifying carbon metabolism to drive synthesis of trehalose.