C. elegans display antipathy behavior towards food after contemporaneous integration of nutritional needs and dietary lipid availability

Organisms utilize sophisticated neurocircuitry to select optimal food sources within their environment. Methylobacterium is a lifespan-promoting bacterial 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 the avoidance behavior toward Methylobacterium identified the AWB and AWC sensory neurons and the odr-1 guanylate cyclase expressed exclusively in those four ciliated neurons as mediators of the antipathy response. Metabolic profiling of the Methylobacterium diet reveals a macromolecular profile enriched in saturated fats and here we show that C. elegans sense and integrate signals related to the type of ingested lipids that subsequently cues food-related behaviors. Moreover, disruption of endogenous lipid metabolism modifies the intensity of antipathy toward Methylobacterium which suggests that the current state of lipid homeostasis influences food preference. Enhanced expression of the sphingolipid degradation enzyme Saposin/spp-9 enhances antipathy behaviors and activation of the sphingosine rheostat and more specifically modulation of the bioactive lipid mediator sphingosine-1-phosphate (S1P) acts as a signal to promote avoidance of Methylobacterium. Taken together, our work reveals that C. elegans modify food choices contemporaneously based on the availability of dietary lipids and the ability to metabolize dietary lipids. HIGHLIGHTSO_LIUncover new molecular mechanisms underlying the decision matrix an animal uses to choose what foods to eat. C_LIO_LIDefine the molecular mechanisms underlying an antipathy behavioral response toward foods after initial ingestion that contemporaneously integrates dietary needs with nutritional profile. C_LIO_LIODR-1 signaling from AWB and AWC ciliated neurons of the C. elegans nervous system mediate the antipathy response to diet. C_LIO_LIManipulation of sphingosine-1-phosphate (S1P) of the sphingosine rheostat controls the intensity of the antipathy behavioral response. C_LIO_LIModulating antipathy behaviors can impact the magnitude of the lifespan-promoting effects of longevity diets. C_LI