Dietary excess triggers accumulation of pro-inflammatory microglia in the mediobasal hypothalamus (MBH), but the components of this microgliosis and its metabolic consequences remain uncertain. Here, we show that microglial inflammatory signaling determines the immunologic response of the MBH to dietary excess and regulates hypothalamic control of energy homeostasis in mice. Either pharmacologically depleting microglia or selectively restraining microglial NF-κB-dependent signaling sharply reduced microgliosis, an effect that includes prevention of MBH entry by bone-marrow-derived myeloid cells, and greatly limited diet-induced hyperphagia and weight gain. Conversely, forcing microglial activation through cell-specific deletion of the negative NF-κB regulator A20 induced spontaneous MBH microgliosis and cellular infiltration, reduced energy expenditure, and increased both food intake and weight gain even in absence of a dietary challenge. Thus, microglial inflammatory activation, stimulated by dietary excess, orchestrates a multicellular hypothalamic response that mediates obesity susceptibility, providing a mechanistic rationale for non-neuronal approaches to treat metabolic diseases.
Pubmed ID: 28683286 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This monoclonal targets CD68
View all literature mentionsThis monoclonal targets Ly-6G
View all literature mentionsThis monoclonal targets Ly-6C
View all literature mentionsThis monoclonal targets Mouse CD11b
View all literature mentionsThis monoclonal targets F4/80 antibody [CI:A3-1]
View all literature mentionsThis polyclonal targets Caveolin
View all literature mentionsThis polyclonal targets Phospho-Stat3 (Tyr705) Antibody detects endogenous levels of Stat3 only when phosphorylated at Tyr705. The antibody does not cross-react with other Stat proteins when phosphorylated on the corresponding tyrosine residue. Does cross-react withPhospho-EGFR
View all literature mentionsThis polyclonal targets RFP
View all literature mentionsThis polyclonal targets Green Fluorescent Protein (GFP)
View all literature mentionsThis monoclonal targets Mouse CD169
View all literature mentionsThis polyclonal targets Iba1
View all literature mentionsMus musculus with name B6.Cg-Tg(Csf1r-EGFP)1Hume/J from IMSR.
View all literature mentionsMus musculus with name B6.Cg-Gt(ROSA)26Sortm14(CAG-tdTomato)Hze/J from IMSR.
View all literature mentionsMus musculus with name B6.129(Cg)-Ccr2tm2.1Ifc/J from IMSR.
View all literature mentionsMus musculus with name C57BL/6-Tg(UBC-GFP)30Scha/J from IMSR.
View all literature mentionsMus musculus with name B6.129P2(Cg)-Cx3cr1tm1Litt/J from IMSR.
View all literature mentionsMus musculus with name B6.129P2(Cg)-Cx3cr1tm2.1(cre/ERT2)Litt/WganJ from IMSR.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentions