| First Author | Lord CC | Year | 2017 |
| Journal | J Clin Invest | Volume | 127 |
| Issue | 9 | Pages | 3402-3406 |
| PubMed ID | 28805659 | Mgi Jnum | J:247717 |
| Mgi Id | MGI:5926674 | Doi | 10.1172/JCI93362 |
| Citation | Lord CC, et al. (2017) The atypical antipsychotic olanzapine causes weight gain by targeting serotonin receptor 2C. J Clin Invest 127(9):3402-3406 |
| abstractText | Atypical antipsychotics such as olanzapine often induce excessive weight gain and type 2 diabetes. However, the mechanisms underlying these drug-induced metabolic perturbations remain poorly understood. Here, we used an experimental model that reproduces olanzapine-induced hyperphagia and obesity in female C57BL/6 mice. We found that olanzapine treatment acutely increased food intake, impaired glucose tolerance, and altered physical activity and energy expenditure in mice. Furthermore, olanzapine-induced hyperphagia and weight gain were blunted in mice lacking the serotonin 2C receptor (HTR2C). Finally, we showed that treatment with the HTR2C-specific agonist lorcaserin suppressed olanzapine-induced hyperphagia and weight gain. Lorcaserin treatment also improved glucose tolerance in olanzapine-fed mice. Collectively, our studies suggest that olanzapine exerts some of its untoward metabolic effects via antagonism of HTR2C. |
