Cell Reports (Jun 2017)
Dectin-1 Activation Exacerbates Obesity and Insulin Resistance in the Absence of MyD88
- Angela Castoldi,
- Vinicius Andrade-Oliveira,
- Cristhiane Favero Aguiar,
- Mariane Tami Amano,
- Jennifer Lee,
- Marcelli Terumi Miyagi,
- Marcela Teatin Latância,
- Tarcio Teodoro Braga,
- Marina Burgos da Silva,
- Aline Ignácio,
- Joanna Darck Carola Correia Lima,
- Flavio V. Loures,
- José Antonio T. Albuquerque,
- Marina Barguil Macêdo,
- Rafael Ribeiro Almeida,
- Jonas W. Gaiarsa,
- Luis A. Luévano-Martínez,
- Thiago Belchior,
- Meire Ioshie Hiyane,
- Gordon D. Brown,
- Marcelo A. Mori,
- Christian Hoffmann,
- Marília Seelaender,
- Willian T. Festuccia,
- Pedro Manoel Moraes-Vieira,
- Niels Olsen Saraiva Câmara
Affiliations
- Angela Castoldi
- Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-900, Brazil
- Vinicius Andrade-Oliveira
- Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-900, Brazil
- Cristhiane Favero Aguiar
- Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-900, Brazil
- Mariane Tami Amano
- Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-900, Brazil
- Jennifer Lee
- Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA
- Marcelli Terumi Miyagi
- Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-900, Brazil
- Marcela Teatin Latância
- Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-900, Brazil
- Tarcio Teodoro Braga
- Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-900, Brazil
- Marina Burgos da Silva
- Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-900, Brazil
- Aline Ignácio
- Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-900, Brazil
- Joanna Darck Carola Correia Lima
- Department of Cellular Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-900, Brazil
- Flavio V. Loures
- Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-900, Brazil
- José Antonio T. Albuquerque
- Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-900, Brazil
- Marina Barguil Macêdo
- Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-900, Brazil
- Rafael Ribeiro Almeida
- Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-900, Brazil
- Jonas W. Gaiarsa
- Tau GC Bioinformatics, Rua Apiacas, 886, São Paulo, SP 05017-020, Brazil
- Luis A. Luévano-Martínez
- Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP 13565-905, Brazil
- Thiago Belchior
- Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-900, Brazil
- Meire Ioshie Hiyane
- Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-900, Brazil
- Gordon D. Brown
- 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
- Marcelo A. Mori
- Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, SP 13083-970, Brazil
- Christian Hoffmann
- 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
- Marília Seelaender
- Department of Cellular Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-900, Brazil
- Willian T. Festuccia
- Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-900, Brazil
- Pedro Manoel Moraes-Vieira
- Department of Genetics, Evolution and Bioagents, Institute of Biology, University of Campinas, Campinas, SP 13083-970, Brazil
- Niels Olsen Saraiva Câmara
- Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-900, Brazil
- DOI
- https://doi.org/10.1016/j.celrep.2017.05.059
- Journal volume & issue
-
Vol. 19,
no. 11
pp. 2272 – 2288
Abstract
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.
Keywords
