@article{b6c6ffe562f0495799f49741a7232097,
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 na{\"i}ve 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 na{\"i}ve 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.",
keywords = "Fecal transfer, Non-aerobic resting metabolic rate, Phage transfer, Risperidone induced weight gain",
author = "Bahr, {Sarah M.} and Weidemann, {Benjamin J.} and Castro, {Ana N.} and Walsh, {John W.} and Orlando deLeon and Burnett, {Colin M.L.} and Pearson, {Nicole A.} and Murry, {Daryl J.} and Grobe, {Justin L.} and Kirby, {John R.}",
note = "Funding Information: This work was supported by grants from the NIH ( HL098276 and HL084207 to JLG, and R01AI108255 to JK), the American Heart Association ( 15SFRN23730000 to JLG), the American Diabetes Association ( 1-14-BS-079 to JLG), the National Science Foundation ( MCB-1244021 to JK), and the University of Iowa Fraternal Order of Eagles' Diabetes Research Center (to JK & JLG). Additional support was provided by the University of Iowa Department of Microbiology . BJW was supported by an undergraduate research fellowship from the American Physiological Society . CMLB was supported by the University of Iowa Medical Student Research Program . ANC was supported by the University of Iowa Dean's Graduate Research Fellowship and an Alfred P. Sloan Foundation Scholarship. OD was supported by an Alfred P. Sloan Foundation Scholarship. Funding Information: The authors gratefully acknowledge the assistance of the University of Iowa Office of Animal Resources for assistance in the project. We also thank Samantha Atkinson for assistance with sequence deposition. Publisher Copyright: {\textcopyright} 2015 The Authors.",
year = "2015",
month = nov,
day = "1",
doi = "10.1016/j.ebiom.2015.10.018",
language = "English (US)",
volume = "2",
pages = "1725--1734",
journal = "EBioMedicine",
issn = "2352-3964",
publisher = "Elsevier BV",
number = "11",
}