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

SM Bahr, BJ Weidemann, AN Castro, JW Walsh… - …, 2015 - thelancet.com
SM Bahr, BJ Weidemann, AN Castro, JW Walsh, O Deleon, CML Burnett, NA Pearson…
EBioMedicine, 2015thelancet.com
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
(80μg/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 naļve recipients, attributable …
Abstract
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 (80μg/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 naļve 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 naļve 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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