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Molecular Biology

Preventing high-fat diet-induced obesity and related metabolic disorders by hydrodynamic transfer of Il-27 gene

International Journal of Obesity volume 47, pages 413–421 (2023)Cite this article

Subjects

Abstract

Background and objectives

Interleukin-27 (IL-27) is a multifaceted heterodimer cytokine that exerts both pro-inflammatory and anti-inflammatory effects under different physiological conditions. IL-27 signaling plays a role in promoting energy expenditure through enhanced thermogenesis. The objective of the study is to determine the functional role of IL-27 in regulating weight gain, and glucose and lipid homeostasis in mice fed a high-fat diet (HFD).

Methods

C57BL/6 mice were hydrodynamically transferred with pLIVE-IL-27 plasmids to achieve elevated level of IL-27 in blood and then kept on a HFD for 8 weeks. The impacts of Il-27 gene transfer on HFD-induced weight gain, adiposity, hepatic lipid accumulation, insulin resistance, glucose homeostasis and the mRNA levels of genes responsible for lipogenesis, glucose homeostasis and proinflammation were assessed by methods of biochemistry, histology, and molecular biology.

Results

Hydrodynamic gene transfer of Il-27 gene resulted in a peak level of serum IL-27 in mice at 14.5 ng/ml 24 h after gene transfer followed by a sustained level at 2 ng/ml. The elevated level of IL-27 blocked HFD-induced fat accumulation and weight gain without reducing food intake. It also prevented metabolic abnormities of liver steatosis and insulin resistance. IL-27 overexpression promoted expression of major thermogenic genes in brown adipose tissues; and attenuated chronic inflammation and macrophage infiltration into white adipose tissues.

Conclusions

The results demonstrate that regulation of IL-27 level could be an effective strategy for management of obesity and obesity-related metabolic diseases.

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Fig. 1: The impact of Il-27 gene transfer on HFD-induced adiposity.
Fig. 2: Il-27 gene transfer blocked hypertrophy of white adipocytes and chronic inflammation in WAT.
Fig. 3: Il-27 gene transfer inhibited fat accumulation in brown adipose tissue.
Fig. 4: Il-27 gene transfer alleviated hyperinsulinemia and insulin resistance.
Fig. 5: Il-27 gene transfer suppressed lipogenesis and lipid accumulation in liver.

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Data availability

All data generated or analyzed during this study are included in the published paper.

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Acknowledgements

The study was supported in part by the Endowment of Panoz Professor of Pharmacy. We thank Dr. Yongjie Ma for technical assistance.

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Authors and Affiliations

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

    Yueze Yang, Huan Liu & Dexi Liu

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  1. Yueze Yang
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Contributions

YY, HL and DL proposed the study and designed the experiments. HL and DL performed the hydrodynamic gene delivery. YY and HL performed animal experiments, qPCR, and western blot analysis. YY performed histological analysis. YY and HL collected and analyzed the data. YY and HL prepared manuscripts under the supervision of DL.

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Correspondence to Dexi Liu.

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Yang, Y., Liu, H. & Liu, D. Preventing high-fat diet-induced obesity and related metabolic disorders by hydrodynamic transfer of Il-27 gene. Int J Obes 47, 413–421 (2023). https://doi.org/10.1038/s41366-023-01293-6

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