Risperidone-induced weight gain is mediated through shifts in the gut microbiome and suppression of energy expenditure

Autor: Sarah M. Bahr, Benjamin J. Weidemann, Ana N. Castro, John W. Walsh, Orlando deLeon, Colin M.L. Burnett, Nicole A. Pearson, Daryl J. Murry, Justin L. Grobe, John R. Kirby
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Zdroj: EBioMedicine, Vol 2, Iss 11, Pp 1725-1734 (2015)
Druh dokumentu: article
ISSN: 2352-3964
DOI: 10.1016/j.ebiom.2015.10.018
Popis: 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.
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