Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Interferon beta overexpression attenuates adipose tissue inflammation and high-fat diet-induced obesity and maintains glucose homeostasis

Gene Therapy volume 24, pages 60–66 (2017)Cite this article

Subjects

Abstract

The worldwide prevalence of obesity is increasing, raising health concerns regarding obesity-related complications. Chronic inflammation has been characterized as a major contributor to the development of obesity and obesity-associated metabolic disorders. The purpose of the current study is to assess whether the overexpression of interferon beta (IFNβ1), an immune-modulating cytokine, will attenuate high-fat diet-induced adipose inflammation and protect animals against obesity development. Using hydrodynamic gene transfer to elevate and sustain blood concentration of IFNβ1 in mice fed a high-fat diet, we showed that the overexpression of Ifnβ1 gene markedly suppressed immune cell infiltration into adipose tissue, and attenuated production of pro-inflammatory cytokines. Systemically, IFNβ1 blocked adipose tissue expansion and body weight gain, independent of food intake. Possible browning of white adipose tissue might also contribute to blockade of weight gain. More importantly, IFNβ1 improved insulin sensitivity and glucose homeostasis. These results suggest that targeting inflammation represents a practical strategy to block the development of obesity and its related pathologies. In addition, IFNβ1-based therapies have promising potential for clinical applications for the prevention and treatment of various inflammation-driven pathologies.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  1. Kanneganti TD, Dixit VD . Immunological complications of obesity. Nat Immunol 2012; 13: 707–712.

    Article  CAS  Google Scholar 

  2. Monteiro R, Azevedo I . Chronic inflammation in obesity and the metabolic syndrome. Mediators Inflamm, e-pub ahead of print 14 July 2010 doi:10.1155/2010/289645.

  3. Donath MY, Dalmas É, Sauter NS, Böni-Schnetzler M . Inflammation in obesity and diabetes: islet dysfunction and dherapeutic dpportunity. Cell Metab 2013; 17: 860–872.

    Article  CAS  Google Scholar 

  4. Parmar S, Platanias LC . Interferons: mechanisms of action and clinical applications. Curr Opin Oncol 2003; 15: 431–439.

    Article  CAS  Google Scholar 

  5. Jacobs LD, Cookfair DL, Rudick RA, Herndon RM, Richert JR, Salazar AM et al. Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Ann Neurol 1996; 39: 285–294.

    Article  CAS  Google Scholar 

  6. Kieseier BC . The mechanism of action of interferon-beta in relapsing multiple sclerosis. CNS Drugs 2011; 25: 491–502.

    Article  CAS  Google Scholar 

  7. Hotamisligil GS, Shargill NS, Spiegelman BM . Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 1993; 259: 87–91.

    Article  CAS  Google Scholar 

  8. Kahn SE, Hull RL, Utzschneider KM . Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 2006; 444: 840–846.

    Article  CAS  Google Scholar 

  9. Ye J . Emerging role of adipose tissue hypoxia in obesity and insulin resistance. Int J Obes 2009; 33: 54–66.

    Article  CAS  Google Scholar 

  10. Ye J, Gao Z, Yin J, He Q . Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice. Am J Physiol Endocrinol Metab 2007; 293: E1118–E11128.

    Article  CAS  Google Scholar 

  11. Hosogai N, Fukuhara A, Oshima K, Miyata Y, Tanaka S, Segawa K et al. Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation. Diabetes 2007; 56: 901–911.

    Article  CAS  Google Scholar 

  12. Mannon PJ, Hornung RL, Yang Z, Yi C, Groden C, Friend J et al. Suppression of inflammation in ulcerative colitis by interferon-beta-1a is accompanied by inhibition of IL-13 production. Gut 2011; 60: 449–455.

    Article  CAS  Google Scholar 

  13. Yoshimura A . Signal transduction of inflammatory cytokines and tumor development. Cancer Sci 2006; 97: 439–447.

    Article  CAS  Google Scholar 

  14. Wang H, Brown J, Garcia CA, Tang Y, Benakanakere MR, Greenway T et al. The role of glycogen synthase kinase 3 in regulating IFN-beta-mediated IL-10 production. J Immunol 2011; 186: 675–684.

    Article  CAS  Google Scholar 

  15. Asadullah K, Sterry W, Volk HD . Interleukin-10 therapy—review of a new approach. Pharmacol Rev 2003; 55: 241–269.

    Article  CAS  Google Scholar 

  16. Shoelson SE, Lee J, Yuan M . Inflammation and the IKK beta/I kappa B/NF-kappa B axis in obesity- and diet-induced insulin resistance. Int J Obes Relat Metab Disord 2003; 27 (Suppl 3): S49–S52.

    Article  CAS  Google Scholar 

  17. Boscá L, Bodelón OG, Hortelano S, Casellas A, Bosch F . Anti-inflammatory action of type I interferons deduced from mice expressing interferon beta. Gene Therapy 2000; 7: 817–825.

    Article  Google Scholar 

  18. Pang C, Gao Z, Yin J, Zhang J, Jia W, Ye J . Macrophage infiltration into adipose tissue may promote angiogenesis for adipose tissue remodeling in obesity. Am J Physiol Endocrinol Metab 2008; 295: E313–E322.

    Article  CAS  Google Scholar 

  19. Christiaens V, Lijnen HR . Angiogenesis and development of adipose tissue. Mol Cell Endocrinol 2010; 318: 2–9.

    Article  CAS  Google Scholar 

  20. Dridi S, Taouis M . Adiponectin and energy homeostasis: consensus and controversy. J Nutr Biochem 2009; 20: 831–839.

    Article  CAS  Google Scholar 

  21. Shoelson SE, Lee J, Goldfine AB . Inflammation and insulin resistance. J Clin Invest 2006; 116: 1793–1801.

    Article  CAS  Google Scholar 

  22. Yadav A, Kataria MA, Saini V, Yadav A . Role of leptin and adiponectin in insulin resistance. Clin Chim Acta 2013; 417: 80–84.

    Article  CAS  Google Scholar 

  23. Burke JD, Platanias LC, Fish EN . Beta interferon regulation of glucose metabolism is PI3K/Akt dependent and important for antiviral activity against coxsackievirus B3. J Virol 2014; 88: 3485–3495.

    Article  CAS  Google Scholar 

  24. Liu F, Song Y, Liu D . Hydrodynamics-based transfection in animals by systemic administration of plasmid DNA. Gene Therapy 1999; 6: 1258–1266.

    Article  CAS  Google Scholar 

  25. Zhang G, Budker V, Wolff JA . High levels of foreign gene expression in hepatocytes after tail vein injections of naked plasmid DNA. Hum Gene Therapy 1999; 10: 1735–1737.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Dr. Megan Morgan for proofreading the manuscript. The study was supported in part by grant from NIH (RO1HL098295).

Author information

Authors and Affiliations

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

    M Alsaggar, M Mills & D Liu

Authors
  1. M Alsaggar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M Mills
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D Liu.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on Gene Therapy website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Alsaggar, M., Mills, M. & Liu, D. Interferon beta overexpression attenuates adipose tissue inflammation and high-fat diet-induced obesity and maintains glucose homeostasis. Gene Ther 24, 60–66 (2017). https://doi.org/10.1038/gt.2016.76

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/gt.2016.76

This article is cited by

Search

Advanced search

Quick links