Acute high-fat diet impairs macrophage-supported intestinal damage resolution

• DOI: 10.1172/jci.insight.164489
• Publication Date: 2022-12-20T18:36:25Z
• Authors: Andrea A. Hill; Myunghoo Kim; Daniel F. Zegarra...; Lin-Chun Chang; Kendra Norwood; Adrien Assié; Wan-Jung H. Wu; Michael C. Renfroe; Hyo Wong Song; Angela M. Major; Buck S. Samuel; Joseph M. Hyser; Randy S. Longman; Gretchen E. Diehl
• Keywords: 0301 basic medicine; Medical Sciences; Neutrophils; Immunology; 610; Diet, High-Fat; Microbiology; Mice; 03 medical and health sciences; Virology; Medical Specialties; Medicine and Health Sciences; and Immunity; Animals; Biological Phenomena; Immunology and Infectious Disease; Cell Phenomena; Macrophages; R; Life Sciences; 600; Lipids; Diet; Interleukin-10; 3. Good health; Intestines; High-Fat; Medical Microbiology; Medicine; Research Article

Chronic exposure to high-fat diets (HFD) worsens intestinal disease pathology, but acute effects of HFD in tissue damage remain unclear. Here, we used short-term feeding a model injury and found sustained with increased cecal dead neutrophil accumulation, along dietary lipid accumulation. Neutrophil depletion rescued enhanced pathology. Macrophages from HFD-treated mice showed reduced capacity engulf neutrophils. Macrophage clearance neutrophils activates critical barrier repair antiinflammatory pathways, including IL-10, which was lost after injury. IL-10 overexpression restored lipids the prevented tethering uptake apoptotic cells Il10 induction. Milk fat globule-EGF factor 8 (MFGE8) is bridging molecule that facilitates macrophage cells. MFGE8 also uptake, demonstrate interfere MFGE8-mediated subsequent production. Our findings promotes pathology by interfering neutrophils, leading unresolved damage.