Temporal specificity of IL-6 knockout in enhancing the thermogenic capability of brown adipose tissue

Although interleukin-6 (IL-6) has been regarded as a homeostatic regulator of fat metabolism, its role in brown adipose thermogenesis remains to be further clarified. By using wild-type (WT) and IL-6-knockout (KO) mice, this study aims to investigate whether IL-6 regulates the thermogenic capability of brown adipose tissue (BAT) at both young and elderly stages. We demonstrated that IL-6 KO enhances BAT thermogenesis at a young age, as evidenced by the increased mRNA and protein expression levels of thermogenic genes, and the elevated interscapular surface temperature. The IL-6-KO enhancement of BAT thermogenesis is associated with improved respiratory exchange ratio (RER) and glucose homeostasis at young stages. However, these improvements disappear in elderly KO mice, which is likely attributable to the highly increased expression of other inflammatory cytokines, such as Tnfα, Il-1β, and Il-10. Our findings indicate that the lack of IL-6 has a temporal-specific contribution to the promotion of BAT thermogenesis.