Abstract | BACKGROUND: METHODOLOGY: Murine obesity models included genetically leptin-deficient ob/ob mice and wild type (WT) mice fed a high fat diet (HFD), that were compared to their lean counterparts. Animals were treated with pharmacological modulators of CB2 receptors. Experiments were also performed in mice knock-out for CB2 receptors (Cnr2 -/-). PRINCIPAL FINDINGS: In both HFD-fed WT mice and ob/ob mice, Cnr2 expression underwent a marked induction in the stromal vascular fraction of epididymal adipose tissue that correlated with increased fat inflammation. Treatment with the CB2 agonist JWH-133 potentiated adipose tissue inflammation in HFD-fed WT mice. Moreover, cultured fat pads isolated from ob/ob mice displayed increased Tnf and Ccl2 expression upon exposure to JWH-133. In keeping, genetic or pharmacological inactivation of CB2 receptors decreased adipose tissue macrophage infiltration associated with obesity, and reduced inductions of Tnf and Ccl2 expressions. In the liver of obese mice, Cnr2 mRNA was only weakly induced, and CB2 receptors moderately contributed to liver inflammation. HFD-induced insulin resistance increased in response to JWH-133 and reduced in Cnr2 -/- mice. Finally, HFD-induced hepatic steatosis was enhanced in WT mice treated with JWH-133 and blunted in Cnr2 -/- mice. CONCLUSION/SIGNIFICANCE:
|
Authors | Vanessa Deveaux, Thomas Cadoudal, Yasukatsu Ichigotani, Fatima Teixeira-Clerc, Alexandre Louvet, Sylvie Manin, Jeanne Tran-Van Nhieu, Marie Pierre Belot, Andreas Zimmer, Patrick Even, Patrice D Cani, Claude Knauf, Remy Burcelin, Adeline Bertola, Yannick Le Marchand-Brustel, Philippe Gual, Ariane Mallat, Sophie Lotersztajn |
Journal | PloS one
(PLoS One)
Vol. 4
Issue 6
Pg. e5844
(Jun 09 2009)
ISSN: 1932-6203 [Electronic] United States |
PMID | 19513120
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
|
Topics |
- Adipocytes
(metabolism)
- Adipose Tissue
(metabolism)
- Animals
- Fatty Liver
(complications, therapy)
- Inflammation
- Insulin Resistance
- Leptin
(metabolism)
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Mice, Transgenic
- Obesity
(complications, therapy)
- Triglycerides
(metabolism)
|