Direct suppression of host gluconeogenesis by Trypanosoma brucei

Direct suppression of host gluconeogenesis by Trypanosoma brucei | 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 Direct suppression of host gluconeogenesis by Trypanosoma brucei Luísa Figueiredo, Abdulbasit Amin, João Colaço, Henrique Machado, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8369960/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract The cause of hypoglycaemia in African trypanosomiasis remains unresolved. We found that infected mice show normal carbohydrate digestion, intestinal glucose absorption, and tissue glucose uptake, but a profound reduction of host glucose production via gluconeogenesis. Liver transcriptomics uncovered coordinated repression of gluconeogenic pathways alongside inflammatory activation. Infection of Rag2⁻/⁻ mice showed that adaptive immunity contributes only minimally to suppression of host gluconeogenesis. In contrast, therapeutic parasite clearance completely restored host glycaemia and gluconeogenesis despite persistent immune activation. These results demonstrate that live parasites directly repress gluconeogenesis in vivo. Using a co-culture assay, we showed that T. brucei is sufficient to directly repress gluconeogenic gene expression in primary hepatocytes in vitro. Finally, we found that providing glycerol in drinking water to infected animals stimulated gluconeogenesis, elevated glycaemia, and improved survival without impacting parasitaemia. This study reveals a previously unrecognised pathogenic strategy in which a eukaryotic parasite directly suppresses host gluconeogenesis. Health sciences/Pathogenesis/Infection Health sciences/Diseases/Infectious diseases/Parasitic infection Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryFile2primersequence.xlsx Supplementary File 2 Supplementaryfile1RNASeq.xlsx Supplementary File 1 Cite Share Download PDF Status: Posted 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. 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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-8369960","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":572541193,"identity":"c4b09a6d-a6fe-40e9-b943-1e4c49bf1586","order_by":0,"name":"Luísa 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