GSE254105 Alternate high fat diet aggravates atherosclerosis through an IL1B- 2 dependent reprogramming of neutrophil progenitors

Contributors : Jean-R émi Lavillegrand ; Marc Diedisheim ; Hafid Ait-OufellaSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusSystemic immune responses induced by chronic hypercholesterolemia contribute to the initiation, progression and complications of atherosclerosis. However, it is common for individuals to change dietary habits over time. The consequences of an alternating high fat diet and the associated variations in plasma cholesterol levels on atherosclerosis are unknown. To address this relevant issue, we developed a novel protocol in atherosclerosis-prone mice that allowed us to compare the effects of alternate versus continuous high fat diet (HFD) on atherosclerosis, while keeping the overall period of exposure to HFD similar between groups. We showed that an alternate HFD lead to accelerated atherosclerosis in Ldlr-/- and Apoe 55 -/- mice compared to continuous HFD. This pro-atherogenic effect of alternate HFD was also observed in Apoe-/-Rag2 57 -/- mice lacking T, B, and NKT cells, ruling out the role of the adaptive immune system in the observed phenotype. Employing various complementary in vivo approaches, we discovered that discontinuing HFD in the alternate group downregulated Runx1, a negative regulator of inflammatory signaling pathways in the myeloid lineage. Consequently, after re61 exposure to HFD, myeloid progenitors were primed to respond to HFD re-exposure by differentiating into IL-1 -producing immature ne...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research