Effect of the cannabinoid receptor-1 antagonist rimonabant on inflammation in mice with diet-induced obesity.
We studied whether cannabinoid receptor (CB1) blockade with rimonabant has an anti-inflammatory effect in obese mice, and whether this effect depends on weight loss and/or diet consumption. High-fat diet (HFD)-induced obese mice were treated orally with rimonabant (HFD-R) or vehicle (HFD-V) for 4 weeks. Paired-feeding was conducted in two additional groups of obese mice to achieve either the same body weight (HFD-BW) or the same HFD intake (HFD DI) as HFD-R. All these groups of mice were maintained on HFD throughout, with mice on normal diet (ND) throughout as lean controls. Rimonabant treatment of obese mice induced marked diet-intake reduction and weight loss during the first week, which was followed by maintenance of low body weight but not diet-intake reduction. Lower HFD intake was required to reach the same degree of weight loss in HFD-BW. HFD-DI had similar weight loss initially, but then started to gain weight, reaching a higher body weight than HFD-R. Despite the same degree of weight loss, HFD-R had less fat mass and lower adipogenic gene expression than HFD-BW. Compared to HFD-V or HFD-DI, HFD-R had reduced inflammation in adipose tissue (AT) and/or liver indicated primarily by lower monocyte chemoattractant protein-1 (MCP-1) levels. However, MCP-1 levels were not significantly different between HFD-R and HFD-BW. In vitro incubation of rimonabant with AT explants did not change MCP-1 levels. Thus, rimonabant induced weight loss in obese mice by diet-intake-dependent and -independent fashions. Rimonabant decreased inflammation in obese mice, possibly through a primary effect on weight reduction.
Wang
Qun
Q
Department of Medicine, Section of Cardiovascular Research, Baylor College of Medicine, Houston, Texas, USA.
Perrard
Xiaoyuan D
XD
Perrard
Jerry L
JL
Mansoori
Amir
A
Smith
C Wayne
CW
Ballantyne
Christie M
CM
Wu
Huaizhu
H
D000273:Adipose Tissue / Q000187:drug effects / Q000473:pathology; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018932:Chemokine CCL2 / Q000097:blood; D004032:Diet / Q000009:adverse effects; D004041:Dietary Fats / Q000009:adverse effects*; D004195:Disease Models, Animal; D002149:Energy Intake / Q000187:drug effects; D007249:Inflammation / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D008099:Liver / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*; D000077285:Rimonabant; D015430:Weight Gain / Q000502:physiology; D015431:Weight Loss / Q000187:drug effects* / Q000502:physiology
D019440:Anti-Obesity Agents; D018932:Chemokine CCL2; D004041:Dietary Fats; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D000077285:Rimonabant