The role of the IL-9‒NLRP3 axis in insulin resistance and adipose tissue inflammation during diet-induced obesity

Early human evidence such as case series or small samples is exploring possible benefits.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Despite the proven beneficial role of type 2 cytokines in diabetes and obesity, IL-9, a predominant Th2 cytokine, has not been investigated in this context. The present study characterized the role of IL-9 signaling in obesity and metabolic dysfunction. We found decreased IL-9 levels in human type 2 diabetes patients and decreased IL-9 signaling in high-fat diet (HFD)-induced obese mice. On the other hand, recombinant IL-9 (rIL-9) treatment reversed insulin insensitivity and inflammation following HFD consumption. IL-9R knockout (KO) mice fed a HFD presented faster weight gain, impaired glucose and insulin tolerance, defective insulin signaling, increased adipocyte size, and decreased energy expenditure. In the adipose tissue of HFD-fed IL-9R KO mice, a significant increase in the number of CD11c+ macrophages and a decrease in the number of RELMα+ macrophages, eosinophils and ILC2s were observed, along with increased TNF, decreased adiponectin production and increased expression of NLRP3. In vitro treatment of human and mouse macrophages with rIL-9 decreased the release of NLRP3-induced IL-1β and IL-18. In vivo treatment of HFD-fed IL-9R KO mice with a pharmacological inhibitor of the NLRP3 inflammasome rescued body weight, insulin sensitivity and adipose tissue inflammation. Mechanistically, the STAT5 protein was found to be important for the IL-9-induced inhibition of the NLR

Evidence level

Early human evidence such as case series or small samples is exploring possible benefits.

Browse all related research

Filter the research library by this study's title keywords, author, or publication year.