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-α (IL-15/sIL-15Rα) on high-fat diet-induced obesity and obesity-associated metabolic disorders. We demonstrate that the multiple hydrodynamic delivery of 2 μg IL-15/sIL-15Rα 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 Pparγ, Cd36, Fabp4, Mgat1, Scd-1 and Fas, and elevated mRNA levels of genes involved in adaptive thermogenesis and fatty acid β-oxidation, such as Ucp1, Ucp3, Pgc-1α, Pgc-1β, Pparα, Pparδ, Cpt1-α and Cpt1-β in obese animals. These results suggest that the overexpression of the Il-15/sIl-15Rα gene is an effective approach in treating diet-induced obesity and its associated metabolic complications.