Metabolic signaling controls intergenerational adaptive responses via peroxisomal catabolism

Metabolic signaling controls intergenerational adaptive responses via peroxisomal catabolism | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Metabolic signaling controls intergenerational adaptive responses via peroxisomal catabolism Thomas Heimbucher, Piyush Gupta, Shivanika Mani, Jeanine Fahrlander, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6522513/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract 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. Biological sciences/Molecular biology/Transcription Biological sciences/Biochemistry/Lipids/Fatty acids Biological sciences/Cell biology/Cell signalling/Lipid signalling Biological sciences/Cell biology/Organelles/Peroxisomes Full Text Additional Declarations There is NO Competing Interest. Supplementary Files TableS1.xlsx Table S1 TableS2.xlsx Table S2 TableS3.xlsx Table S3 SupplementaryInformation.pdf Supplementary Information Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6522513","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":487062099,"identity":"143e8b5f-75ce-4cc6-89fb-7f8f0863524e","order_by":0,"name":"Thomas 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