Objective: Consumption of a modern Western-type high-fat low-fiber diet increases the risk of obesity. However, how a host responds to such a diet, especially during the early period of dietary transition from a previous low-fat and fiber-rich diet, remains poorly explored.
Methods: Wild-type C57BL/6 mice were fed a normal chow diet or a high-fat diet. Enteric glial cell (EGC) activation was detected through quantitative real-time PCR (qRT-PCR), immunoblotting and immunohistology analysis. Fluorocitrate or genetic deletion of glial fibrillary acidic protein (GFAP)-positive glial-intrinsic myeloid differentiation factor 88 (Myd88) was used to inhibit EGC activation, and the effect of a high-fat diet on obesity was further investigated. The role of MYD88-dependent sensing of commensal products in adipocyte was observed to analyze the effect of obesity.
Results: A dietary shift from a normal chow diet to a high-fat diet in mice induced a transient early-phase emergence of a GFAP-positive EGC network in the lamina propria of the ileum, accompanied with an increase in glial-derived neurotrophic factor production. Inhibition of glial cell activity blocked this response. GFAP-positive glial Myd88 knockout mice gained less body weight after high-fat diet (HFD) feeding than littermate controls. In contrast, adipocyte deletion of Myd88 in mice had no effect on weight gain but instead exacerbated glucose intolerance. Furthermore, short-term fluorocitrate intervention during HFD feeding attenuated body weight gain.
Conclusions: Our findings indicate that EGCs are early responders to intestinal ecosystem changes and the GFAP-positive glial Myd88 signaling participates in regulating obesity.
Keywords: Diet; enteric glial cell; fluorocitrate; gut; metabolic disorder; neurotrophic factor; obesity; myeloid differentiation primary response 88.