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Transfer of Obesity via the Gut Microbiome is Mediated Specifically through Suppression of Non‐Aerobic Resting Metabolism
Author(s) -
Grobe Justin,
Bahr Sarah,
Weidemann Benjamin,
Burnett Colin,
Pearson Nicole,
DeLeon Orlando,
Murry Daryl,
Kirby John
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.857.2
Subject(s) - weight gain , chemistry , endocrinology , medicine , microbiome , basal metabolic rate , zoology , body weight , biology , bioinformatics
Risperidone (RISP) is an antipsychotic drug that causes robust weight gain, and we previously found that it alters the gut microbiome in humans and mice. We hypothesize that the gut microbiome mediates the metabolic effects of RISP. C57BL/6J mice were treated with RISP (0.12 mg/day in drinking water) for 9 weeks. RISP increased weight gain (+0.4 g/wk vs vehicle, P<0.05), but had no effect on food intake (vehicle n=5, 4.0±0.1, vs RISP n=5, 4.0±0.1 g/day), or digestive efficiency determined by bomb calorimetry (77±2 vs 80±1% consumed). Therefore we conclude that reduced energy expenditure explains weight gain associated with RISP treatment. To examine causality, the gut microbiome from vehicle or RISP‐treated mice was transferred to a naïve cohort over 2 weeks by gavage of aqueous‐extracted fecal material (resulting in 84 ng/day RISP transfer, 0.07% of the original dose). Total resting metabolic rate (RMR) and aerobic RMR were measured at thermoneutrality (30C) using a combined direct calorimeter + respirometer. Mice receiving vehicle transfer (n=6) exhibited no change in total or aerobic RMR (+0.004±0.006, +0.005±0.001 kcal/hr). Mice receiving RISP transfer (n=7) exhibited a massive 16% reduction in total RMR (–0.018±0.008 kcal/hr, P<0.05), but no change in aerobic RMR (+0.001±0.001 kcal/hr). We conclude that RISP causes weight gain through suppressed non‐aerobic RMR, via modulation of the gut microbiome.