Gut Microbiota-Derived Leucine Promotes Cold-Induced Atherosclerosis by Inhibiting Macrophage Efferocytosis

Gut Microbiota-Derived Leucine Promotes Cold-Induced Atherosclerosis by Inhibiting Macrophage Efferocytosis | 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 Gut Microbiota-Derived Leucine Promotes Cold-Induced Atherosclerosis by Inhibiting Macrophage Efferocytosis Yongtai Gong, Sen Yan, Ning Fang, Yun Zhang, Ning Zhang, Long Li, and 18 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4666347/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 Cold exposure has been shown to impact the development of atherosclerotic cardiovascular disease (ASCVD) and is associated with dysbiosis in the gut microbiota. In our study, we found that cold exposure increased both plaque area and plaque instability in ApoE−/− mice. Further analysis revealed that gut microbiota and microbial metabolites play a crucial role in cold-related atherosclerosis. Specifically, following cold exposure, there was a notable decrease in the abundance of Lactobacillus. johnsonii (L. johnsonii) in the intestinal tract and an increase in plasma leucine levels. Supplementation with L. johnsonii alleviated cold-related atherosclerosis in ApoE−/− mice. Importantly, our in vivo and in vitro studies demonstrated that leucine reduces efferocytosis by decreasing the expression of Gas6 in macrophages, thereby promoting the progression of cold-related atherosclerosis. These findings highlight the central role of gut microbiota and microbial metabolites in modulating efferocytosis during cold-related atherosclerosis. The L. johnsonii-leucine-Gas6 pathway holds promise as a potential therapeutic target for addressing cold-related atherosclerosis. Health sciences/Cardiology/Cardiovascular biology/Cardiovascular diseases/Vascular diseases/Atherosclerosis Biological sciences/Microbiology/Bacteria/Bacterial host response Full Text Additional Declarations There is NO Competing Interest. 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-4666347","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":331150428,"identity":"f158bf4a-ee88-4d5c-90c9-4f4f4f157158","order_by":0,"name":"Yongtai 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