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

Author(s):Show less -

Castoldi, Angela ; Andrade-Oliveira, Vinicius ; Aguiar, Cristhiane Favero ; Amano, Mariane Tami ; Lee, Jennifer ; Miyagi, Marcelli Terumi ; Latancia, Marcela Teatin ; Braga, Tarcio Teodoro ; da Silva, Marina Burgos ; Ignacio, Aline ; Carola Correia Lima, Joanna Darck ; Loures, Flavio V. ; Albuquerque, Jose Antonio T. ; Macedo, Marina Barguil ; Almeida, Rafael Ribeiro ; Gaiarsa, Jonas W. ; Luevano-Martinez, Luis A. ; Belchior, Thiago ; Hiyane, Meire Ioshie ; Brown, Gordon D. ; Mori, Marcelo A. ; Hoffmann, Christian ; Seelaender, Marilia ; Festuccia, Willian T. ; Moraes-Vieira, Pedro Manoel ; Saraiva Camara, Niels Olsen

• Document type: Journal article
• Source: CELL REPORTS; v. 19, n. 11, p. 2272-2288, JUN 13 2017.
• Web of Science Citations: 8

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 ther-apeutic implications as a biomarker for metabolic dysregulation in humans. (AU)

• FAPESP's process: 15/18121-4 - Relationship between obesity and intestinal lamina propria cells function in insulin resistance development
• Grantee: Angela Castoldi
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 11/15682-4 - Sepsis and Obesity: study of the relationship between obesity and immune regulation in an experimental model of sepsis
• Grantee: Angela Castoldi
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 12/02270-2 - New cellular, molecular and immunological mechanisms involved in acute and chronic renal injury: the search for new therapeutical approaches
• Grantee: Niels Olsen Saraiva Câmara
• Support Opportunities: Research Projects - Thematic Grants