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