Fat food exacerbates post-prandial hypothalamic inflammation involving GFAP+ cells and microglia

Abstract

In humans, obesity was associated with brain inflammation and glial cell proliferation. Studies in rodents showed that glial cell proliferation occurs within 24 hours of high-fat diet (HFD) consumption, before obesity development. This proliferation was mainly observed in the hypothalamus (HT), a crucial brain structure for controlling body weight. Therefore, we sought to characterize the post-prandial HT inflammatory response to 1-3-6 hours exposure to a standard diet and HFD. HFD exposure increased gene expression of astrocyte and microglial marker (GFAP and Iba1) compare to standard treated mice and induced morphological modifications of microglial cells in HT. This remodeling was associated with higher expression of inflammatory genes and differential activation of hypothalamic neuropeptides involved in energy balance regulation. DREADD and PLX5622 technologies, used to modulate GFAP-positive or microglial cells activity respectively, showed that both glial cell types are involved in hypothalamic post-prandial inflammation, but in a different time frame and with a diet specificity Thus, an exacerbated post-prandial inflammation in brain might predispose individuals to obesity and needs to be characterized to address this worldwide crisis.