Artikel
Characterization of glial reaction to high-fat diet in mouse and human hypothalamus
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Veröffentlicht: | 25. August 2015 |
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Gliederung
Text
Diets high in fat are known to cause inflammation in the periphery as well as the central nervous system. In peripheral adipose tissue, it has been shown that inflammation is primarily mediated by macrophages that are recruited to the tissue. Similarly, a recent study demonstrated reactive microgliosis in the hypothalamus of mice fed a high-fat diet. We aimed to dissect the glial reaction to diets high in fat in a detailed manner by analyzing gene expression and cell number in the hypothalamus of mice fed HFD for 3 days or 8 weeks. We detected a significant increase in microglia cells and astrocyte reactivity in the hypothalamus after prolonged HFD feeding. However, this increase was not accompanied by an increase in pro-inflammatory markers, but rather by an anti-inflammatory reaction. Furthermore, we demonstrate that the detected increase in Iba1+ myeloid cells upon HFD is due to proliferation of endogenous microglia and not due to infiltrating macrophages. Histological analysis of post-mortem human brain tissue of obese versus non-obese individuals reveals that similar to the situation in the mouse brain, gliosis is also evident in the hypothalamus of obese individuals. Finally, to analyze whether this gliosis leads to profound changes in the hypothalamus area we conducted a region-specific genome-wide methylation analysis.