| Autor: |
Lord CC; Division of Hypothalamic Research, Department of Internal Medicine, and., Wyler SC; Division of Hypothalamic Research, Department of Internal Medicine, and., Wan R; Division of Hypothalamic Research, Department of Internal Medicine, and., Castorena CM; Division of Hypothalamic Research, Department of Internal Medicine, and., Ahmed N; Division of Hypothalamic Research, Department of Internal Medicine, and., Mathew D; Division of Hypothalamic Research, Department of Internal Medicine, and., Lee S; Division of Hypothalamic Research, Department of Internal Medicine, and., Liu C; Division of Hypothalamic Research, Department of Internal Medicine, and.; Department of Neuroscience, and., Elmquist JK; Division of Hypothalamic Research, Department of Internal Medicine, and.; Department of Pharmacology, UT Southwestern Medical Center, Dallas, Texas, USA. |
| Abstrakt: |
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. |
