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 anti-inflammatory pathways including IL10, which was lost after acute HFD feeding and intestinal injury. IL10 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.

Dietary long-chain fatty acids promote colitis by regulating palmitoylation of STAT3 through CD36-mediated endocytosis

“…This diet is characterized by its high content of saturated LCFAs, refined sugars, salt, and artificial sweeteners [ 2 ]. Earlier research has demonstrated that an HFD can promote experimental colitis [ 3 , 4 , 35 ]. However, the precise underlying mechanisms are still under investigation.…”

Comprehensive Proteomic Analysis of HCoV-OC43 Virions and Virus-Modulated Extracellular Vesicles

“…EIF3C is one of many translational initiation factors that modulate hepatitis C gene expression (81, 82) and conceivably also modulate coronaviruses. MFGE8 is a multifunctional protein that has been associated with tissue repair (83) and binds the SARS-CoV-2 receptors expressed in the placenta (84). RAB7A is a small GTPase that modulates the intracellular vesicular transport of proteins along the endocytic pathway (85) that can be used by some coronaviruses to enter cells (86–88) and is modulated by SARS-CoV-2 (89–92).…”