Metabolic signaling controls intergenerational adaptive responses via peroxisomal catabolism

Transmission of stress-associated metabolic signals and resources across generations can induce strong adaptive responses in offspring, promoting their survival and supporting species continuity. However, the mechanisms driving the intergenerational transmission of signals, the signalling molecules and their effectors in progeny are largely unknown. Here, we identify signalling inputs converging on the serum-and-glucocorticoid-inducible kinase SGK-1 as regulators of adaptive, intergenerational lipid metabolic processes in cold stress (CS). We find that adaptive responses benefiting offspring involve a reallocation of lipid resources from the soma to the germline, which is at the cost of maternal survival after CS. By controlling peroxisomal catabolism and lipid mobilization to oocytes, SGK-1 and its downstream transcriptional effector PQM-1 regulate the availability of peroxisomal dicarboxylic acids (DCAs), which are essential for intergenerational signalling to offspring. DCA availability for oocytes is determined by the peroxisomal catabolic enzyme ECH-9, which is tightly regulated by the SGK-1/PQM-1 signalling axis. Remarkably, a single DCA metabolite, the C16-DCA hexadecanedioic acid, can function as an intergenerational signalling molecule. Hexadecanedioic acid is transferred by lipoproteins to oocytes and induces the nuclear receptor NHR-49 in embryos to promote offspring survival in CS. Our data support a model in which a peroxisomal lipid metabolite can induce an intergenerational adaptive response in progeny.