Macrophage CGI-58/IL-1β pathway prevents overnutrition- induced chronic inflammation and Insulin resistance

Proinflammatory activation of macrophages is causally linked to obesity-related chronic inflammation and insulin resistance (IR). However, the metabolic factors mediating macrophage activation in response to overnutrition is not fully understood. We identified comparative gene identification-58 (CGI-58), a well characterized lipolytic co-activator of adipose triglyceride lipase, as a novel suppressor of proinflammatory cytokine production in macrophages. Specifically, in response to overnutrition, macrophage CGI-58 deficiency activates NLRP3-inflammasome pathway to initiate a vicious cycle (IL-1β－SOCS3－FOXO1－IL-1β), which further induces systemic chronic inflammation and IR.