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Anja Schmidt-Christensen

Assistant researcher

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Deficiency in plasmacytoid dendritic cells and type I interferon signalling prevents diet-induced obesity and insulin resistance in mice

Author

  • Tine D. Hannibal
  • Anja Schmidt-Christensen
  • Julia Nilsson
  • Nina Fransén-Pettersson
  • Lisbeth Hansen
  • Dan Holmberg

Summary, in English

Aims/hypothesis: Obesity is associated with glucose intolerance and insulin resistance and is closely linked to the increasing prevalence of type 2 diabetes. In mouse models of diet-induced obesity (DIO) and type 2 diabetes, an increased fat intake results in adipose tissue expansion and the secretion of proinflammatory cytokines. The innate immune system not only plays a crucial role in obesity-associated chronic low-grade inflammation but it is also proposed to play a role in modulating energy metabolism. However, little is known about how the modulation of metabolism by the immune system may promote increased adiposity in the early stages of increased dietary intake. Here we aimed to define the role of type I IFNs in DIO and insulin resistance. Methods: Mice lacking the receptor for IFN-α (IFNAR−/−) and deficient in plasmacytoid dendritic cells (pDCs) (B6.E2-2fl/fl.Itgax-cre) were fed a diet with a high fat content or normal chow. The mice were analysed in vivo and in vitro using cellular, biochemical and molecular approaches. Results: We found that the development of obesity was inhibited by an inability to respond to type I IFNs. Furthermore, the development of obesity and insulin resistance in this model was associated with pDC recruitment to the fatty tissues and liver of obese mice (a 4.3-fold and 2.7-fold increase, respectively). Finally, we demonstrated that the depletion of pDCs protects mice from DIO and from developing obesity-associated metabolic complications. Conclusions/interpretation: Our results provide genetic evidence that pDCs, via type I IFNs, regulate energy metabolism and promote the development of obesity.

Department/s

  • Autoimmunity

Publishing year

2017-06-28

Language

English

Pages

2033-2041

Publication/Series

Diabetologia

Volume

60

Issue

10

Document type

Journal article

Publisher

Springer

Topic

  • Endocrinology and Diabetes

Keywords

  • Adipose tissue
  • Obesity
  • pDCs
  • Type I interferons

Status

Published

Research group

  • Autoimmunity

ISBN/ISSN/Other

  • ISSN: 0012-186X