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

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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

• Tipo de documento: Artigo Científico
• Fonte: CELL REPORTS; v. 19, n. 11, p. 2272-2288, JUN 13 2017.
• Citações Web of Science: 8

Resumo

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)

• Processo FAPESP: 15/18121-4 - Estudo da relação entre a obesidade e a função das células da lâmina própria intestinal no desenvolvimento da resistência à insulina
• Beneficiário: Angela Castoldi
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 11/15682-4 - Sepse e obesidade: estudo da relação entre a obesidade e a regulação imunológica em um modelo de sepse experimental
• Beneficiário: Angela Castoldi
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 12/02270-2 - Novos mecanismos celulares, moleculares e imunológicos das lesões renais agudas e crônicas: busca por novas estratégias terapêuticas
• Beneficiário: Niels Olsen Saraiva Câmara
• Modalidade de apoio: Auxílio à Pesquisa - Temático