Acute high-fat diet impairs macrophage-supported intestinal damage resolution Journal Article
| Authors: | Hill, A. A.; Kim, M.; Zegarra-Ruiz, D. F.; Chang, L. C.; Norwood, K.; Assié, A.; Wu, W. J. H.; Renfroe, M. C.; Song, H. W.; Major, A. M.; Samuel, B. S.; Hyser, J. M.; Longman, R. S.; Diehl, G. E. |
| Article Title: | Acute high-fat diet impairs macrophage-supported intestinal damage resolution |
| Abstract: | 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 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 Il10 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 Il10 production. Our findings demonstrate that HFD promotes intestinal pathology by interfering with macrophage clearance of dead neutrophils, leading to unresolved tissue damage. © 2023, Hill et al. |
| Keywords: | signal transduction; controlled study; protein expression; nonhuman; mouse; animal; animals; mice; animal tissue; apoptosis; interleukin 10; lipid; animal experiment; physiology; lipids; macrophage; macrophages; intestine; intestines; bioaccumulation; tissue repair; intestine injury; interleukin-10; lipid transport; lipid diet; fat intake; lipid storage; leukocyte activation; male; female; article; lactadherin; intestine tissue; diet, high-fat |
| Journal Title: | JCI Insight |
| Volume: | 8 |
| Issue: | 3 |
| ISSN: | 2379-3708 |
| Publisher: | Amer Soc Clinical Investigation Inc |
| Date Published: | 2023-02-08 |
| Start Page: | e164489 |
| Language: | English |
| DOI: | 10.1172/jci.insight.164489 |
| PUBMED: | 36538527 |
| PROVIDER: | scopus |
| PMCID: | PMC9977439 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- MSK corresponding author is Gretchen Diehl -- Export Date: 1 March 2023 -- Source: Scopus |
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