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

Publication date: 13 June 2017
Source:Cell Reports, Volume 19, Issue 11
Author(s): 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
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.

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Teaser

Castoldi et al. identify a role for Dectin-1 in obesity and insulin resistance (IR). Dectin-1 KO mice have decreased CD11c+ adipose tissue (AT) macrophages (ATMs) and are protected from obesity and IR. Increased expression of Dectin-1 in AT correlates with obesity.


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