Figure 2. High-fat diet consumption reversibly activates hippocampal microglia.

(A), Stereological quantification of microglia in the hippocampal dentate gyrus reveals that mice consuming high-fat diet throughout the experiment (HFD/HFD) have significantly more microglia with 1–2 primary processes (‘Simple’). By contrast, mice exposed to 3 months of HFD, then switched to low-fat diet (LFD) chow for 2 months (HFD/LFD) have fewer simple microglia than HFD/HFD mice. There was no effect of HFD or diet reversal on microglia with 3 or more primary processes (‘Complex’). (B), Micrographs depict peroxidase immunolabeling for the microglial marker ionized calcium binding adapter protein 1 (IBA1) on hippocampal sections from mice in the indicated conditions. Higher magnification panels show Simple and Complex microglia from mice in each condition. For low magnification images, scalebar=100μm. For high magnification panels, scalebar=10μm. (C), Expression of the classical activation marker major histocompatibility complex II (MHCII) is sparse in IBA1+ cells from LFD/LFD and HFD/LFD mice, regardless of their morphology, but HFD/HFD mice exhibit robust induction of MHCII in anatomically simple microglia. (D), Confocal micrographs of IBA1/MHCII fluorescence, with DAPI nuclear counterstain. Scalebar=5μm. For all graphs, error bars represent the s.e.m. and asterisks (*) denote statistical significance at p<0.05 following one-way ANOVA with post hoc Bonferroni-correct t-tests.