Deficiency of Stat1 in CD11c+ Cells Alters Adipose Tissue Inflammation and Improves Metabolic Dysfunctions in Mice Fed a High-Fat Diet
Autor: | Jerry L. Perrard, Antu Kalathookunnel Antony, Huaizhu Wu, Christie M. Ballantyne, Zeqin Lian, Hua Liu, Lothar Hennighausen, Pradip K. Saha, Xiaoyuan Dai Perrard, Sean M. Hartig, Aaron R. Cox |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
medicine.medical_specialty biology Chemistry Endocrinology Diabetes and Metabolism Skeletal muscle Interleukin Adipose tissue CD11c 030209 endocrinology & metabolism Inflammation medicine.disease 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Insulin resistance medicine.anatomical_structure Endocrinology Downregulation and upregulation Internal medicine Internal Medicine medicine biology.protein STAT1 medicine.symptom |
Zdroj: | Diabetes. 70:720-732 |
ISSN: | 1939-327X 0012-1797 |
Popis: | CD11c+ macrophages/dendritic cells (MDCs) are increased and display the 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 the 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 a high-fat diet (HFD). Compared with littermate controls, cKO mice fed an HFD (16 weeks) had reductions in MDC (mainly CD11c+ macrophage) M1-like polarization and interferon-γ–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 demonstrate 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. |
Databáze: | OpenAIRE |
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