Dectin-1 activation exacerbates obesity and insulin resistance in absence of MyD88. mouse gut metagenome

The underlying mechanism by which MyD88 regulates the development of obesity, meta-inflammation and insulin resistant (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 in proinflammatory CD11c+ AT macrophages (ATMs). Similarly, a Dectin-1 agonist worsened glucose homeostasis in mice. Dectin-1 expression is increased in AT from obese individuals and correlates with increased BMI and triglycerides. Dectin-1 antagonist improved glucose homeostasis and decreased CD11c+ ATMs in chow and HFD fed MyD88 KO mice. Dectin-1 KO mice were protected from diet-induced obesity (DIO) and IR development and had reduced CD11c+ ATM polarization. Together, our data indicate that Dectin-1 regulates AT inflammation by promoting CD11c+ ATMs polarization in the absence of MyD88 and identifies a new role for Dectin-1 in chronic inflammatory states, such as obesity.