Hydrodynamic delivery of IL-38 gene alleviates obesity-induced inflammation and insulin resistance.

Abstract Obesity is associated with a chronic inflammatory response. Interleukin (IL)-38 is a poorly characterized cytokine of the IL-1 family with anti-inflammatory activity. The role of IL-38 in obesity-induced inflammation and insulin resistance remains unknown. In this study, we investigated the effects of IL-38 expression by hydrodynamic-based gene delivery on high-fat diet-induced obesity in mice. Transfer of plasmid DNA encoding IL-38 reduced weight gain, liver fat content, adipose tissue weight, and obesity-induced insulin resistance compared with administration of a control plasmid. Moreover, IL-38 gene delivery inhibited the production of inflammatory mediators including IL-1β, IL-6, and monocyte chemotactic protein-1. These results suggest that IL-38 is a potential new target for the treatment of obesity. Highlights • IL-38 inhibits HFD-induced obesity. • IL-38 reduces HFD-induced systemic insulin resistance. • IL-38 inhibits HFD-induced hepatic fat accumulation and liver damage. • IL-38 inhibits HFD induced-hypertrophy in adipocytes. • IL-38 suppresses HFD-induced inflammatory cytokines production. [ABSTRACT FROM AUTHOR]