IL-15/sIL-15Rα gene transfer induces weight loss and improves glucose homeostasis in obese mice

Obesity and its associated metabolic problems are a major public health issue. The objective of the current study is to investigate the therapeutic effects of interleukin 15/soluble interleukin 15 receptor-alpha (IL-15/sIL-15R alpha) on high-fat diet-induced obesity and obesity-associated metabolic disorders. We demonstrate that the multiple hydrodynamic delivery of 2 mu g IL-15/sIL-15R alpha plasmid results in numerous beneficial effects, including a reduction of body weight and fat mass, an alleviation of fatty liver, an improvement in glucose homeostasis and insulin sensitivity in obese mice. These effects are accompanied by a suppressed expression of genes involved in lipid accumulation and lipogenesis, including Ppar gamma, Cd36, Fabp4, Mgat1, Scd-1 and Fas, and elevated mRNA levels of genes involved in adaptive thermogenesis and fatty acid beta-oxidation, such as Ucp1, Ucp3, Pgc-1 alpha, Pgc-1 beta, Ppar alpha, Ppar delta, Cpt1-alpha and Cpt1-beta in obese animals. These results suggest that the overexpression of the Il-15/sIl-15R alpha gene is an effective approach in treating diet-induced obesity and its associated metabolic complications.