Defective intestinal repair after short-term high fat diet due to loss of efferocytosis

Abstract

Defective tissue repair is a hallmark of many inflammatory disorders including, inflammatory bowel disease (IBD). While it is clear that high fat diets (HFD) can exacerbate inflammatory disease by increasing inflammation, the direct effect of lipids on tissue homeostasis and repair remains undefined. We show here that short term exposure to HFD directly impairs barrier repair after intestinal epithelial damage by interfering with recognition and uptake of apoptotic neutrophils by intestinal macrophages. Apoptotic neutrophil uptake induces macrophage IL-10 production, which is lacking after intestinal damage in the context of HFD. Overexpression of IL-10 rescues repair defects after HFD treatment, but not if epithelial cells lack the IL-10 receptor, highlighting the key role of IL-10 in barrier repair. These findings demonstrate a previously unidentified mechanism by which dietary lipids directly interfere with homeostatic processes required to maintain tissue integrity.