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Here, we used short-term HFD feeding in a model of intestinal injury and found sustained damage with increased cecal dead neutrophil accumulation, along with dietary lipid accumulation. Neutrophil depletion rescued enhanced pathology. Macrophages from HFD-treated mice showed reduced capacity to engulf dead neutrophils. Macrophage clearance of dead neutrophils activates critical barrier repair and antiinflammatory pathways, including IL-10, which was lost after acute HFD feeding and intestinal injury. IL-10 overexpression restored intestinal repair after HFD feeding and intestinal injury. Macrophage exposure to lipids from the HFD prevented tethering and uptake of apoptotic cells and\n                    <jats:italic>Il10<\/jats:italic>\n                    induction. Milk fat globule-EGF factor 8 (MFGE8) is a bridging molecule that facilitates macrophage uptake of dead cells. MFGE8 also facilitates lipid uptake, and we demonstrate that dietary lipids interfere with MFGE8-mediated macrophage apoptotic neutrophil uptake and subsequent\n                    <jats:italic>Il10<\/jats:italic>\n                    production. Our findings demonstrate that HFD promotes intestinal pathology by interfering with macrophage clearance of dead neutrophils, leading to unresolved tissue damage.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.164489","type":"journal-article","created":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T13:36:25Z","timestamp":1671543385000},"source":"Crossref","is-referenced-by-count":29,"title":["Acute high-fat diet impairs macrophage-supported intestinal damage resolution"],"prefix":"10.1172","volume":"8","author":[{"given":"Andrea A.","family":"Hill","sequence":"first","affiliation":[{"name":"Department of Pathology and Immunology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myunghoo","family":"Kim","sequence":"additional","affiliation":[{"name":"Alkek Center for Metagenomics and Microbiome Research and the Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, 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