Abstract
ObjectiveIL-15 is an inflammatory cytokine secreted by many cell types. IL-15 is also produced during physical exercise by skeletal muscle and has been reported to reduce weight gain in mice. Contrarily, our findings on IL-15 knockout (KO) mice indicate that IL-15 promotes obesity. The aim of this study is to investigate the mechanisms underlying the pro-obesity role of IL-15 in adipose tissues.MethodsControl and IL-15 KO mice were maintained on high fat diet (HFD) or normal control diet. After 16 weeks, body weight, adipose tissue and skeletal mass, serum lipid levels and gene/protein expression in the adipose tissues were evaluated. The effect of IL-15 on thermogenesis and oxygen consumption was also studied in primary cultures of adipocytes differentiated from mouse preadipocyte and human stem cells.ResultsOur results show that IL-15 deficiency prevents diet-induced weight gain and accumulation of lipids in visceral and subcutaneous white and brown adipose tissues. Gene expression analysis also revealed elevated expression of genes associated with adaptive thermogenesis in the brown and subcutaneous adipose tissues of IL-15 KO mice. Accordingly, oxygen consumption was increased in the brown adipocytes from IL-15 KO mice. In addition, IL-15 KO mice showed decreased expression of pro-inflammatory mediators in their adipose tissues.ConclusionsAbsence of IL-15 results in decreased accumulation of fat in the white adipose tissues and increased lipid utilization via adaptive thermogenesis. IL-15 also promotes inflammation in adipose tissues that could sustain chronic inflammation leading to obesity-associated metabolic syndrome.
Highlights
Chronic inflammation is an important mediator of obesity-associated metabolic syndrome [1,2,3]
Our results show that IL-15 deficiency prevents diet-induced weight gain and accumulation of lipids in visceral and subcutaneous white and brown adipose tissues
Gene expression analysis revealed elevated expression of genes associated with adaptive thermogenesis in PLOS ONE | DOI:10.1371/journal.pone
Summary
Chronic inflammation is an important mediator of obesity-associated metabolic syndrome [1,2,3]. Lipid-induced inflammatory mediators establish a vicious positive feedback loop and sustain chronic inflammation in obese WAT, leading to loss of insulin sensitivity and type 2 diabetes (T2D) [2]. While the role of inflammatory mediators in promoting insulin resistance in the obese WAT is well documented, it is not clear how inflammation affects the functions of BAT. Catecholamines from alternatively activated macrophages promote adaptive thermogenesis [12]. Given that increasing the activity of BAT and induction of brite cells in WAT are considered to be a promising approach to decrease the fat mass in obese individuals [13,14,15], it is important to understand the role of inflammation in regulating adaptive thermogenesis
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