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

Gene Therapy volume 23, pages 349–356 (2016)Cite this article

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Abstract

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.

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Acknowledgements

We thank Dr Barbara K Felber (NCI) for generously providing us with AG209 DP muIL-15sRα+IL-15 plasmid and Mrs Francisca Burnley for proofreading the manuscript. The study was supported in part by grants from NIH (RO1 EB007357 and RO1 HL098295).

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Authors and Affiliations

  1. Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA, USA

    H Sun, Y Ma, M Gao & D Liu

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Correspondence to D Liu.

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Sun, H., Ma, Y., Gao, M. et al. IL-15/sIL-15Rα gene transfer induces weight loss and improves glucose homeostasis in obese mice. Gene Ther 23, 349–356 (2016). https://doi.org/10.1038/gt.2016.4

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