Dectin-1 Activation Exacerbates Obesity and Insulin Resistance in the Absence of MyD88

Cell Reports

Luis A. Luévano-Martínez¹  Marcelo A. Mori²  Joanna Darck Carola Correia Lima³  Marília Seelaender³  Pedro Manoel Moraes-Vieira⁴  Marina Burgos da Silva⁵  Cristhiane Favero Aguiar⁵  José Antonio T. Albuquerque⁵  Angela Castoldi⁵  Vinicius Andrade-Oliveira⁵  Niels Olsen Saraiva Câmara⁵  Mariane Tami Amano⁵  Marcelli Terumi Miyagi⁵  Marcela Teatin Latância⁵  Flavio V. Loures⁵  Marina Barguil Macêdo⁵  Tarcio Teodoro Braga⁵  Rafael Ribeiro Almeida⁵  Meire Ioshie Hiyane⁵  Aline Ignácio⁵  Thiago Belchior⁶  Willian T. Festuccia⁶  Jennifer Lee⁷  Christian Hoffmann⁸  Gordon D. Brown⁹  Jonas W. Gaiarsa^1,10 

[1] Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP 13565-905, Brazil;Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, SP 13083-970, Brazil;Department of Cellular Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-900, Brazil;Department of Genetics, Evolution and Bioagents, Institute of Biology, University of Campinas, Campinas, SP 13083-970, Brazil;Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-900, Brazil;Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-900, Brazil;Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA;Food Research Center - FoRC, Department of Food Sciences and Experimental Nutrition, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP 05508-080, Brazil;MRC Centre for Medical Mycology, Aberdeen Fungal Group, School of Medicine, Medical Sciences & Nutrition, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB24 3FX, UK;Tau GC Bioinformatics, Rua Apiacas, 886, São Paulo, SP 05017-020, Brazil;

关键词: MyD88;    Dectin-1;    obesity;    insulin resistance;    inflammation;    macrophage;    adipose tissue;   

DOI  :  10.1016/j.celrep.2017.05.059

来源: DOAJ

【 摘 要 】

The underlying mechanism by which MyD88 regulates the development of obesity, metainflammation, and insulin resistance (IR) remains unknown. Global deletion of MyD88 in high-fat diet (HFD)-fed mice resulted in increased weight gain, impaired glucose homeostasis, elevated Dectin-1 expression in adipose tissue (AT), and proinflammatory CD11c+ AT macrophages (ATMs). Dectin-1 KO mice were protected from diet-induced obesity (DIO) and IR and had reduced CD11c+ AT macrophages. Dectin-1 antagonist improved glucose homeostasis and decreased CD11c+ AT macrophages in chow- and HFD-fed MyD88 KO mice. Dectin-1 agonist worsened glucose homeostasis in MyD88 KO mice. Dectin-1 expression is increased in AT from obese individuals. Together, our data indicate that Dectin-1 regulates AT inflammation by promoting CD11c+ AT macrophages in the absence of MyD88 and identify a role for Dectin-1 in chronic inflammatory states, such as obesity. This suggests that Dectin-1 may have therapeutic implications as a biomarker for metabolic dysregulation in humans.

【 授权许可】

Unknown