Risperidone-induced weight gain is mediated through shifts in the gut microbiome and suppression of energy expenditure.
Risperidone-induced weight gain is mediated through shifts in the gut microbiome and suppression of energy expenditure.
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DOI：
10.1016/j.ebiom.2015.10.018
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发表时间：
2015-11
期刊：
影响因子：
11.1
通讯作者：
Kirby JR
中科院分区：
文献类型：
--
作者：
Bahr SM;Weidemann BJ;Castro AN;Walsh JW;deLeon O;Burnett CM;Pearson NA;Murry DJ;Grobe JL;Kirby JR
利培酮是第二代抗精神病药，会导致体重增加。我们假设利培酮诱导的肠道微生物组变化在机制上参与了其代谢后果。用利培酮（80 μg/天）治疗的野生型雌性C57 BL/6 J小鼠表现出显著的过量体重增加，这是由于能量消耗减少，这与肠道微生物组的改变相关。利培酮处理小鼠的粪便移植导致未处理受体的总静息代谢率降低16%，这归因于非需氧代谢的抑制。利培酮对厌氧培养的粪便细菌的抑制作用大于需氧培养的。最后，利培酮处理小鼠的粪便噬菌体部分的移植足以导致幼稚受体的体重过度增加，再次通过减少能量消耗。总的来说，这些数据突出了肠道微生物组在长期使用利培酮后体重增加中的主要作用，并特别暗示了该机制中非有氧静息代谢的调节。利培酮诱导的体重增加与肠道微生物组的改变相关。利培酮诱导的体重增加是由于能量消耗受到抑制。利培酮处理的微生物群或噬菌体的转移抑制能量消耗。能量消耗的减少归因于非有氧静息代谢。利培酮处理的微生物群的转移抑制非有氧静息代谢。利培酮越来越多地用于精神疾病，并且已知会导致人类体重增加。这项研究表明，利培酮诱导的体重增加与小鼠肠道细菌组成的变化相关。观察到的体重增加是通过抑制能量消耗介导的，特别是通过降低非有氧静息代谢率。通过将肠道微生物群或相关噬菌体（细菌病毒）从利培酮处理的动物转移到未处理的动物，可以重现这种效果。因此，肠道细菌及其相关病毒可以影响静息代谢率的变化，导致体重增加。
Risperidone is a second-generation antipsychotic that causes weight gain. We hypothesized that risperidone-induced shifts in the gut microbiome are mechanistically involved in its metabolic consequences. Wild-type female C57BL/6J mice treated with risperidone (80 μg/day) exhibited significant excess weight gain, due to reduced energy expenditure, which correlated with an altered gut microbiome. Fecal transplant from risperidone-treated mice caused a 16% reduction in total resting metabolic rate in naïve recipients, attributable to suppression of non-aerobic metabolism. Risperidone inhibited growth of cultured fecal bacteria grown anaerobically more than those grown aerobically. Finally, transplant of the fecal phage fraction from risperidone-treated mice was sufficient to cause excess weight gain in naïve recipients, again through reduced energy expenditure. Collectively, these data highlight a major role for the gut microbiome in weight gain following chronic use of risperidone, and specifically implicates the modulation of non-aerobic resting metabolism in this mechanism. Risperidone-induced weight gain correlates with an altered gut microbiome. Risperidone-induced weight gain occurs due to suppressed energy expenditure. Transfer of risperidone-treated microbiota or phage suppresses energy expenditure. Reduction in energy expenditure is attributable to non-aerobic resting metabolism. Transfer of risperidone-treated microbiota suppresses non-aerobic resting metabolism. Risperidone is increasingly used for psychiatric disorders and is known to cause robust weight gain in humans. This study demonstrates that risperidone-induced weight gain correlates with alterations in the bacterial composition of the gut in mice. The observed weight gain is mediated through suppression of energy expenditure, specifically by reducing non-aerobic resting metabolic rate. The effect can be reproduced by transferring the gut microbiota or associated bacteriophage (bacterial viruses) from risperidone-treated animals to naïve animals. Thus, gut bacteria and their associated viruses can affect changes in resting metabolic rates leading to weight gain.