title: Risperidone-induced weight gain is mediated through shifts in the gut microbiome and suppression of energy expenditure.
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 (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.
authors: Sarah M
authors: SM
authors: Bahr
authors: Benjamin J
authors: BJ
authors: Weidemann
authors: Ana N
authors: AN
authors: Castro
authors: John W
authors: JW
authors: Walsh
authors: Orlando
authors: O
authors: deLeon
authors: Colin M L
authors: CM
authors: Burnett
authors: Nicole A
authors: NA
authors: Pearson
authors: Daryl J
authors: DJ
authors: Murry
authors: Justin L
authors: JL
authors: Grobe
authors: John R
authors: JR
authors: Kirby
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects*; D000069467:Fecal Microbiota Transplantation; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D054892:Metagenome; D056186:Metagenomics / Q000379:methods; D051379:Mice; D018967:Risperidone / Q000008:administration & dosage / Q000494:pharmacology*; D015430:Weight Gain / Q000187:drug effects*; D015262:Xenobiotics / Q000494:pharmacology
chemical_list: D014150:Antipsychotic Agents; D015262:Xenobiotics; D018967:Risperidone
keywords: Fecal transfer; Gut microbiome; Non-aerobic resting metabolic rate; Phage transfer; Risperidone induced weight gain; Suppression of energy expenditure