Effect of the Cannabinoid Receptor‐1 Antagonist Rimonabant on Inflammation in Mice With Diet‐Induced Obesity

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Abstract
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.

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