Advanced

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

Hannibal, Tine D. LU ; Schmidt-Christensen, Anja LU ; Nilsson, Julia LU ; Fransén-Pettersson, Nina LU ; Hansen, Lisbeth LU and Holmberg, Dan LU (2017) In Diabetologia
Abstract

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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
Adipose tissue, Obesity, pDCs, Type I interferons
in
Diabetologia
pages
9 pages
publisher
Springer Verlag
external identifiers
  • scopus:85025134423
  • wos:000408770300020
ISSN
0012-186X
DOI
10.1007/s00125-017-4341-0
language
English
LU publication?
yes
id
941416d1-f63a-4871-8f8a-d5d1fdeb29bc
date added to LUP
2017-08-30 09:25:45
date last changed
2018-01-16 13:23:54
@article{941416d1-f63a-4871-8f8a-d5d1fdeb29bc,
  abstract     = {<p>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<sup>−/−</sup>) and deficient in plasmacytoid dendritic cells (pDCs) (B6.E2-2<sup>fl/fl</sup>.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.</p>},
  author       = {Hannibal, Tine D. and Schmidt-Christensen, Anja and Nilsson, Julia and Fransén-Pettersson, Nina and Hansen, Lisbeth and Holmberg, Dan},
  issn         = {0012-186X},
  keyword      = {Adipose tissue,Obesity,pDCs,Type I interferons},
  language     = {eng},
  month        = {06},
  pages        = {9},
  publisher    = {Springer Verlag},
  series       = {Diabetologia},
  title        = {Deficiency in plasmacytoid dendritic cells and type I interferon signalling prevents diet-induced obesity and insulin resistance in mice},
  url          = {http://dx.doi.org/10.1007/s00125-017-4341-0},
  year         = {2017},
}