Volatile diacetyl triggers rapid fmo-2 expression through DHAP-glycerol shunt induction

C. elegans can locate ephemeral food sources by sensing bacterially-derived volatiles. However, whether these olfactory cues can also trigger anticipatory nutrient-responsive programs remains unknown. Using unbiased transcriptomics and metabolomics, we discover that fasting worms exposed to the volatile food cue diacetyl rapidly induce expression of enzymes in the DHAP-Glycerol shunt, a metabolic pathway at the intersection of glycolysis and glycerolipid biosynthesis. We demonstrate that this pathway, known to be activated by glucotoxicity and hyperosmotic stress, is also modulated by food availability. Shunt induction requires the MDT-15 transcription factor and drives rapid metabolic remodeling, characterised by the accumulation of glycerol and phosphatidylglycerols. When food deprivation persists, the shunts activity triggers expression of the dietary restriction marker fmo-2, promoting thermotolerance and food-seeking behaviours. Our findings reveal that volatile diacetyl can rapidly modulate gene expression in C. elegans, providing new insights into the DHAP-Glycerol shunt function in metabolic homeostasis.