Dietary ingredient change induces a transient MyD88-dependent mucosal enteric glial cell response and promotes obesity
Open Access
- 7 November 2022
- journal article
- research article
- Published by Taylor & Francis Ltd in Nutritional Neuroscience
- Vol. 26 (12), 1183-1193
- https://doi.org/10.1080/1028415x.2022.2142129
Abstract
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. 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. 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. Our findings indicate that EGCs are early responders to intestinal ecosystem changes and the GFAP-positive glial Myd88 signaling participates in regulating obesity.Keywords
Funding Information
- National Natural Science Foundation of China (81770853, 82002157)
- Priority Academic Program Development of Jiangsu Higher Education Institutions (KYLX14-1448)
- Natural Science Foundation of the Higher Education Institutions of Jiangsu Province, China (16KJB310016)
- Starting Foundation for Talents of Xuzhou Medical University (D2016029)
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