Lactose Stimulation of Hepatic De Novo Lipogenesis Implicates Non-Canonical Pathways of Galactose Metabolism: A Randomised Crossover Trial

Lactose Stimulation of Hepatic De Novo Lipogenesis Implicates Non-Canonical Pathways of Galactose Metabolism: A Randomised Crossover Trial | 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 Lactose Stimulation of Hepatic De Novo Lipogenesis Implicates Non-Canonical Pathways of Galactose Metabolism: A Randomised Crossover Trial Javier Gonzalez, Steven Carter, Bruno Spellanzon, Elspeth Johnson, and 13 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9346481/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 Dietary sugars differentially influence hepatic lipid metabolism, yet the metabolism of galactose—the monosaccharide unique to lactose—remains poorly defined in humans. Here, using stable isotope tracers and lipoprotein fractionation in a randomized crossover trial, we show that lactose ingestion robustly stimulates hepatic de novo lipogenesis and exaggerates postprandial lipaemia to an extent comparable with sucrose and markedly greater than a glucose polymer. Lactose-induced lipaemia arises from coordinated increases in endogenous, dietary and newly synthesized fatty acids and is associated with elevated lactate production but not fructose-associated uric acid accumulation. Strikingly, the magnitude of lactose-stimulated lipogenesis is inversely related to postprandial glycaemia, and modest galactose co-ingestion attenuates glycaemic responses to a starch meal. These findings reveal non-canonical pathways of galactose metabolism that couple lipogenesis to reduced glycaemic exposure and challenge the prevailing view that galactose-containing sugars are metabolically equivalent to glucose-based carbohydrates. Biological sciences/Physiology/Metabolism/Fat metabolism Biological sciences/Physiology/Metabolism Sugars lipids metabolism fructose galactose glucose Full Text Additional Declarations There is NO Competing Interest. 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-9346481","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":626189728,"identity":"4af480a3-e9f0-47c8-a85a-626300cb9d37","order_by":0,"name":"Javier 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