TY - JOUR
T1 - CD40L deficiency attenuates diet-induced adipose tissue inflammation by impairing immune cell accumulation and production of pathogenic IgG-antibodies
AU - Wolf, Dennis
AU - Jehle, Felix
AU - Rodriguez, Alexandra Ortiz
AU - Dufner, Bianca
AU - Hoppe, Natalie
AU - Colberg, Christian
AU - Lozhkin, Andrey
AU - Bassler, Nicole
AU - Rupprecht, Benjamin
AU - Wiedemann, Ansgar
AU - Hilgendorf, Ingo
AU - Stachon, Peter
AU - Willecke, Florian
AU - Febbraio, Mark
AU - Binder, Christoph J.
AU - Bode, Christoph
AU - Zirlik, Andreas
AU - Peter, Karlheinz
PY - 2012/3/8
Y1 - 2012/3/8
N2 - Background: Adipose tissue inflammation fuels the metabolic syndrome. We recently reported that CD40L - an established marker and mediator of cardiovascular disease - induces inflammatory cytokine production in adipose cells in vitro. Here, we tested the hypothesis that CD40L deficiency modulates adipose tissue inflammation in vivo. Methodology/Principal Findings: WT or CD40L -/- mice consumed a high fat diet (HFD) for 20 weeks. Inflammatory cell recruitment was impaired in mice lacking CD40L as shown by a decrease of adipose tissue macrophages, B-cells, and an increase in protective T-regulatory cells. Mechanistically, CD40L-deficient mice expressed significantly lower levels of the pro-inflammatory chemokine MCP-1 both, locally in adipose tissue and systemically in plasma. Moreover, levels of pro-inflammatory IgG-antibodies against oxidized lipids were reduced in CD40L -/- mice. Also, circulating low-density lipoproteins and insulin levels were lower in CD40L -/- mice. However, CD40L -/- mice consuming HFD were not protected from the onset of diet-induced obesity (DIO), insulin resistance, and hepatic steatosis, suggesting that CD40L selectively limits the inflammatory features of diet-induced obesity rather than its metabolic phenotype. Interestingly, CD40L -/- mice consuming a low fat diet (LFD) showed both, a favorable inflammatory and metabolic phenotype characterized by diminished weight gain, improved insulin tolerance, and attenuated plasma adipokine levels. Conclusion: We present the novel finding that CD40L deficiency limits adipose tissue inflammation in vivo. These findings identify CD40L as a potential mediator at the interface of cardiovascular and metabolic disease.
AB - Background: Adipose tissue inflammation fuels the metabolic syndrome. We recently reported that CD40L - an established marker and mediator of cardiovascular disease - induces inflammatory cytokine production in adipose cells in vitro. Here, we tested the hypothesis that CD40L deficiency modulates adipose tissue inflammation in vivo. Methodology/Principal Findings: WT or CD40L -/- mice consumed a high fat diet (HFD) for 20 weeks. Inflammatory cell recruitment was impaired in mice lacking CD40L as shown by a decrease of adipose tissue macrophages, B-cells, and an increase in protective T-regulatory cells. Mechanistically, CD40L-deficient mice expressed significantly lower levels of the pro-inflammatory chemokine MCP-1 both, locally in adipose tissue and systemically in plasma. Moreover, levels of pro-inflammatory IgG-antibodies against oxidized lipids were reduced in CD40L -/- mice. Also, circulating low-density lipoproteins and insulin levels were lower in CD40L -/- mice. However, CD40L -/- mice consuming HFD were not protected from the onset of diet-induced obesity (DIO), insulin resistance, and hepatic steatosis, suggesting that CD40L selectively limits the inflammatory features of diet-induced obesity rather than its metabolic phenotype. Interestingly, CD40L -/- mice consuming a low fat diet (LFD) showed both, a favorable inflammatory and metabolic phenotype characterized by diminished weight gain, improved insulin tolerance, and attenuated plasma adipokine levels. Conclusion: We present the novel finding that CD40L deficiency limits adipose tissue inflammation in vivo. These findings identify CD40L as a potential mediator at the interface of cardiovascular and metabolic disease.
UR - http://www.scopus.com/inward/record.url?scp=84857804227&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0033026
DO - 10.1371/journal.pone.0033026
M3 - Article
AN - SCOPUS:84857804227
SN - 1932-6203
VL - 7
JO - PLoS ONE
JF - PLoS ONE
IS - 3
M1 - e33026
ER -