Effect of the cannabinoid receptor-1 antagonist rimonabant on inflammation in mice with diet-induced obesity.
Effect of the cannabinoid receptor-1 antagonist rimonabant on inflammation in mice with diet-induced obesity.
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DOI：
10.1038/oby.2010.213
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发表时间：
2011-03
期刊：
影响因子：
--
通讯作者：
Wu H
中科院分区：
文献类型：
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作者：
Wang Q;Perrard XD;Perrard JL;Mansoori A;Smith CW;Ballantyne CM;Wu H
我们研究了用利莫那班阻断CB1是否对肥胖小鼠有抗炎作用，以及这种作用是否依赖于体重减轻和/或饮食消耗。采用高脂饮食(HFD)诱导肥胖小鼠，分别给予利莫那班(HFD-R)和赋形剂(HFD-V)灌胃治疗4周。对另外两组肥胖小鼠进行配对喂养，以达到与HFD-R相同的体重(HFD-BW)或相同的HFD摄入量(HFD-DI)。所有这些组的小鼠都一直服用HFD，而一直以正常饮食的小鼠作为瘦身对照。利莫那班对肥胖小鼠的治疗在第一周导致显著的饮食摄入量减少和体重减轻，随后保持低体重，但不减少饮食摄入量。较低的HFD摄入量才能达到与HFD-BW相同的减重程度。HFD-DI最初有类似的体重减轻，但后来开始增加体重，达到比HFD-R更高的体重。尽管体重减轻程度相同，但HFD-R的脂肪质量和成脂基因表达水平低于HFD-BW。与HFD-V或HFD-DI相比，HFD-R主要通过降低单核细胞趋化蛋白-1(MCP-1)水平来减轻脂肪组织(AT)和/或肝脏的炎症。然而，HFD-R组和HFD-BW组的MCP-1水平无显著差异。利莫那班与AT外植体体外孵育不改变MCP-1水平。因此，利莫那班通过饮食摄入量依赖和非依赖的方式诱导肥胖小鼠体重减轻。利莫那班减轻肥胖小鼠的炎症，可能是通过减轻体重的主要作用。
We studied whether 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 2 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 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.