Prevention of Diet-Induced Obesity Effects on Body Weight and Gut Microbiota in Mice Treated Chronically with Δ9-Tetrahydrocannabinol.
Prevention of Diet-Induced Obesity Effects on Body Weight and Gut Microbiota in Mice Treated Chronically with Δ9-Tetrahydrocannabinol.
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DOI：
10.1371/journal.pone.0144270
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Sharkey KA
中科院分区：
文献类型：
--
作者：
Cluny NL;Keenan CM;Reimer RA;Le Foll B;Sharkey KA
大麻素CB 1受体激动剂的急性给药，或大麻的摄入，诱导短期的食欲过盛。然而，与非大麻使用者相比，经常使用大麻的人肥胖的发生率较低。肠道微生物群影响宿主代谢，在肥胖状态下观察到微生物谱的改变。肠道微生物群通过对内源性大麻素系统的作用来改变脂肪生成。本研究调查了长期THC给药对饮食诱导肥胖（DIO）和瘦小鼠体重和肠道微生物群的影响。每天用载体或THC（2 mg/kg持续3周，4 mg/kg持续另外1周）处理成年雄性DIO和瘦小鼠。纵向测量体重、脂肪量、能量摄入、自发活动、全肠道运输和肠道微生物群。THC减少DIO小鼠的体重增加、脂肪量增加和能量摄入，但对瘦小鼠没有影响。DIO诱导的选择肠道微生物群的变化在长期施用THC的小鼠中被阻止。THC对瘦小鼠或DIO小鼠的自发活动或整个肠道运输没有影响。长期THC治疗减少了能量摄入，并防止了高脂肪饮食诱导的体重和肥胖增加;这些作用不太可能是镇静或胃肠道转运改变的结果。肠道微生物群的变化可能有助于肥胖症中慢性THC诱导的体重作用。
Acute administration of cannabinoid CB1 receptor agonists, or the ingestion of cannabis, induces short-term hyperphagia. However, the incidence of obesity is lower in frequent cannabis users compared to non-users. Gut microbiota affects host metabolism and altered microbial profiles are observed in obese states. Gut microbiota modifies adipogenesis through actions on the endocannabinoid system. This study investigated the effect of chronic THC administration on body weight and gut microbiota in diet-induced obese (DIO) and lean mice. Adult male DIO and lean mice were treated daily with vehicle or THC (2mg/kg for 3 weeks and 4 mg/kg for 1 additional week). Body weight, fat mass, energy intake, locomotor activity, whole gut transit and gut microbiota were measured longitudinally. THC reduced weight gain, fat mass gain and energy intake in DIO but not lean mice. DIO-induced changes in select gut microbiota were prevented in mice chronically administered THC. THC had no effect on locomotor activity or whole gut transit in either lean or DIO mice. Chronic THC treatment reduced energy intake and prevented high fat diet-induced increases in body weight and adiposity; effects that were unlikely to be a result of sedation or altered gastrointestinal transit. Changes in gut microbiota potentially contribute to chronic THC-induced actions on body weight in obesity.