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

Angela Castoldi (Corresponding Author), 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 C. Lima, Flávio 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 BrownMarcelo A. Mori, Christian Hoffmann, Marília Seelaender, Willian T. Festuccia, Pedro Manoel Moraes-Vieira, Niels Olsen Saraiva Câmara

Research output: Contribution to journalArticle

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Abstract

Highlights
•MyD88 absence upregulates Dectin-1 in adipose tissue (AT) and AT macrophages (ATMs)
•Dectin-1 inhibition decreases CD11c+ ATMs and protects mice from insulin resistance (IR)
•Dectin-1 activation increases CD11c+ ATMs and worsens IR
•Obese humans have increased Dectin-1 expression in AT
Summary
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.
Original languageEnglish
Pages (from-to)2272-2288
Number of pages7
JournalCell Reports
Volume19
Issue number11
DOIs
Publication statusPublished - 13 Jun 2017

Keywords

  • MyD88
  • Dectin-1
  • insulin resistance
  • inflammation
  • macrophage
  • adipose tissue

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