Deficiency in adipocyte chemokine receptor CXCR4 exacerbates obesity and compromises thermoregulatory responses of brown adipose tissue in a mouse model of diet-induced obesity

FASEB J. 2014 Oct;28(10):4534-50. doi: 10.1096/fj.14-249797. Epub 2014 Jul 11.


The chemokine receptor CXCR4 is expressed on adipocytes and macrophages in adipose tissue, but its role in this tissue remains unknown. We evaluated whether deficiency in either adipocyte or myeloid leukocyte CXCR4 affects body weight (BW) and adiposity in a mouse model of high-fat-diet (HFD)-induced obesity. We found that ablation of adipocyte, but not myeloid leukocyte, CXCR4 exacerbated obesity. The HFD-fed adipocyte-specific CXCR4-knockout (AdCXCR4ko) mice, compared to wild-type C57BL/6 control mice, had increased BW (average: 52.0 g vs. 35.5 g), adiposity (average: 49.3 vs. 21.0% of total BW), and inflammatory leukocyte content in white adipose tissue (WAT), despite comparable food intake. As previously reported, HFD feeding increased uncoupling protein 1 (UCP1) expression (fold increase: 3.5) in brown adipose tissue (BAT) of the C57BL/6 control mice. However, no HFD-induced increase in UCP1 expression was observed in the AdCXCR4ko mice, which were cold sensitive. Thus, our study suggests that adipocyte CXCR4 limits development of obesity by preventing excessive inflammatory cell recruitment into WAT and by supporting thermogenic activity of BAT. Since CXCR4 is conserved between mouse and human, the newfound role of CXCR4 in mouse adipose tissue may parallel the role of this chemokine receptor in human adipose tissue.

Keywords: adaptive thermogenesis; chemotactic cytokine system.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism*
  • Adipose Tissue, Brown / cytology
  • Adipose Tissue, Brown / metabolism*
  • Adipose Tissue, Brown / physiology
  • Adipose Tissue, White / cytology
  • Adipose Tissue, White / metabolism
  • Adipose Tissue, White / physiology
  • Animals
  • Diet, High-Fat / adverse effects
  • Ion Channels / genetics
  • Ion Channels / metabolism
  • Leukocytes / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Obesity / etiology
  • Obesity / metabolism*
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / metabolism*
  • Thermogenesis*
  • Uncoupling Protein 1


  • CXCR4 protein, mouse
  • Ion Channels
  • Mitochondrial Proteins
  • Receptors, CXCR4
  • UCP1 protein, human
  • Ucp1 protein, mouse
  • Uncoupling Protein 1