A lipid-sensitive food choice behavior influences aging outcomes from a longevity-promoting diet.

Organisms utilize sophisticated neurocircuitry to select optimal food sources. Methylobacterium is a lifespan-promoting diet for C. elegans that drives faster development and longevity; however, after ingestion, C. elegans consistently choose any other food option available. A screen for genetic regulators of this avoidance behavior toward Methylobacterium identified the AWB/AWC sensory neurons and the odr-1 guanylate cyclase expressed in those four ciliated neurons as mediators of the aversive response. Metabolic profiling of the Methylobacterium diet reveals enrichment for saturated fats, and here, we show that C. elegans sense and integrate signals related to these ingested lipids that subsequently cue food-related behaviors. Moreover, disruption of endogenous lipid metabolism modifies the intensity of the avoidance from Methylobacterium, suggesting the current state of lipid homeostasis influences food preference. Taken together, our work reveals that C. elegans modify food choice contemporaneously based in part on the chemosensory capacity to detect and utilize dietary lipids, which has longevity-promoting consequences.