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Deficiency of Stat1 in CD11c+ Cells Alters Adipose Tissue Inflammation and Improves Metabolic Dysfunctions in Mice Fed High-Fat Diet
figure
posted on 2020-12-15, 23:12 authored by Antu Antony, Zeqin Lian, Xiaoyuan Dai Perrard, Jerry Perrard, Hua Liu, Aaron R. Cox, Pradip Saha, Lothar Hennighausen, Sean M. Hartig, Christie M. Ballantyne, Huaizhu WuCD11c+ macrophages/dendritic cells (MDCs) are
increased and display classically activated M1-like phenotype in obese adipose
tissue (AT) and may contribute to AT inflammation and insulin resistance. Stat1
is a key transcription factor for MDC polarization into M1-like phenotype. Here,
we examined the role of Stat1 in obesity-induced AT MDC polarization and
inflammation and insulin resistance using mice with specific knockout of Stat1
in MDCs (cKO). Stat1 was upregulated and phosphorylated, indicating activation,
early and persistently in AT and AT MDCs of wild-type mice fed high-fat diet (HFD).
Compared to littermate controls, cKO mice fed HFD (16 weeks) had reductions in MDC
(mainly CD11c+ macrophage) M1-like polarization and interferon-g–expressing T helper type 1 (Th1) cells, but increases in interleukin-5–expressing Th2
cells and eosinophils in perigonadal and
inguinal AT, and enhanced inguinal AT browning, with increased energy
expenditure. cKO mice compared with controls also had significant reductions in
triglyceride content in the liver and skeletal muscle and exhibited improved insulin sensitivity and
glucose tolerance. Taken together, our results demonstrated that Stat1 in MDCs
plays an important role in obesity-induced MDC M1-like polarization and AT
inflammation and contributes to insulin resistance and metabolic dysfunctions
in obese mice.