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

Abstract

SUMMARYOrganisms utilize sophisticated neurocircuitry to select optimal food sources within their environment.Methylobacteriumis a lifespan-promoting bacterial diet forC. elegansthat drives faster development and longevity, however after ingestion,C. elegansconsistently choose any other food option available. A screen for genetic regulators of the avoidance behavior towardMethylobacteriumidentified the AWB and AWC sensory neurons and theodr-1guanylate cyclase expressed exclusively in those four ciliated neurons as mediators of the antipathy response. Metabolic profiling of theMethylobacteriumdiet reveals a macromolecular profile enriched in saturated fats and here we show thatC. eleganssense 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 towardMethylobacteriumwhich suggests that the current state of lipid homeostasis influences food preference. Enhanced expression of the sphingolipid degradation enzyme Saposin/spp-9enhances 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 ofMethylobacterium. Taken together, our work reveals thatC. elegansmodify food choices contemporaneously based on the availability of dietary lipids and the ability to metabolize dietary lipids.HIGHLIGHTSUncover new molecular mechanisms underlying the decision matrix an animal uses to choose what foods to eat.Define the molecular mechanisms underlying an antipathy behavioral response toward foods after initial ingestion that contemporaneously integrates dietary needs with nutritional profile.ODR-1 signaling from AWB and AWC ciliated neurons of theC. elegansnervous system mediate the antipathy response to diet.Manipulation of sphingosine-1-phosphate (S1P) of the sphingosine rheostat controls the intensity of the antipathy behavioral response.Modulating antipathy behaviors can impact the magnitude of the lifespan-promoting effects of longevity diets.