Original Article | Published:

Animal Models

Blocking high-fat diet-induced obesity, insulin resistance and fatty liver by overexpression of Il-13 gene in mice

International Journal of Obesity volume 39, pages 12921299 (2015) | Download Citation

Abstract

Objectives:

The objective of this study was to assess the activity of anti-inflammatory cytokine IL-13 (interleukin-13) in blocking high-fat diet-induced obesity and obesity-associated insulin resistance and liver steatosis.

Methods:

C57BL/6 mice were fed a high-fat diet and received hydrodynamic delivery of plasmids carrying the mouse Il-13 or Gfp (control) gene. IL-13 blood protein levels, food consumption and body weight of mice were continuously monitored for 8 weeks. Fat and lean masses of treated and control animals were determined at the end of the experiment. Serum concentrations of glucose, insulin and lipids were determined, and mRNA levels of macrophage marker genes in adipose tissue and genes involved in energy metabolism were examined using real-time PCR. Glucose tolerance and insulin sensitivity tests were performed to determine glucose homeostasis. Histochemistry and lipid assays were performed to determine the hepatic lipid accumulation.

Results:

Blood concentration of IL-13 was 20 ng ml−1 1 week after gene delivery and declined with time. Overexpression of Il-13 prevented high-fat diet-induced weight gain without affecting food consumption. Mice that underwent Il-13 gene transfer showed regular body weight and normal serum concentrations of glucose and insulin, and less lipid accumulation in the liver. Overexpression of Il-13 blocked macrophage infiltration in adipose tissue and suppressed high-fat diet-induced expression of inflammatory F4/80, Cd68 and Mcp1, and elevated the expression of Ucp1 (uncoupling protein 1 gene) responsible for energy expenditure.

Conclusion:

These results suggest that suppression of diet-induced inflammation by IL-13 is an effective strategy in preventing diet-induced obesity and obesity-associated insulin resistance and fatty liver.

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Acknowledgements

We thank Miss Ryan Fugett for English editing of the manuscript. This work was supported in part by a grant from NIH (RO1HL098295).

Author information

Affiliations

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

    • P Darkhal
    • , M Gao
    • , Y Ma
    •  & D Liu

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Competing interests

The authors declare no conflict of interest.

Corresponding author

Correspondence to D Liu.

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DOI

https://doi.org/10.1038/ijo.2015.52

Supplementary Information accompanies this paper on International Journal of Obesity website (http://www.nature.com/ijo)

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