Interleukin-15 contributes to the regulation of murine adipose tissue and human adipocytes

Abstract

An alarming global rise in the prevalence of obesity and its contribution to the development of chronic diseases is a serious health concern. Recently, obesity has been described as a chronic low-grade inflammatory condition, influenced by both adipose tissue and immune cells suggesting proinflammatory cytokines may play a role in its etiology. Here we examined the effects of interleukin-15 (IL-15) on adipose tissue and its association with obesity. Over expression of IL-15 (IL-15tg) was associated with lean body condition whereas lack of IL-15 (IL-15(-/-)) results in significant increase in weight gain without altering appetite. Interestingly, there were no differences in proinflammatory cytokines such as IL-6 and tumor necrosis factor-alpha (TNF-alpha) in serum between the three strains of mice. In addition, there were significant numbers of natural killer (NK) cells in fat tissues from IL-15tg and B6 compared to IL-15(-/-) mice. IL-15 treatment results in significant weight loss in IL-15(-/-) knockout and diet-induced obese mice independent of food intake. Fat pad cross-sections show decreased pad size with over expression of IL-15 is due to adipocyte shrinkage. IL-15 induces weight loss without altering food consumption by affecting lipid deposition in adipocytes. Treatment of differentiated human adipocytes with recombinant human IL-15 protein resulted in decreased lipid deposition. In addition, obese patients had significantly lower serum IL-15 levels when compared to normal weight individuals. These results clearly suggest that IL-15 may be involved in adipose tissue regulation and linked to obesity.