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Olanzapine-induced weight gain and increased visceral adiposity is blocked by melatonin replacement therapy in rats
Murray A Raskind1, Brianna L Burke, Norman J Crites
1VA Puget Sound Health Care System, Mental Illness Research, Education and Clinical Center, Seattle, WA 98108, USA.
Abstract:
The atypical antipsychotic drug olanzapine increases body weight and visceral adiposity in schizophrenia. In rats, aging-associated increased body weight and visceral adiposity are reversed by administration of the pineal hormone melatonin. We asked if melatonin similarly would reverse olanzapine-induced increased weight and visceral adiposity in rats. Four groups (n=11/group) of female rats (240-250 g) were treated for 8 weeks with olanzapine, melatonin, olanzapine+melatonin, or vehicle alone in drinking water. Body weight and food and water consumption were determined weekly, locomotor activity at weeks 3 and 6, and nocturnal plasma melatonin concentration at week 7. At week 8, the rats were killed and visceral (perirenal, retroperitoneal, omental, and mesenteric) fat pads dissected and weighed. Olanzapine treatment reduced nocturnal plasma melatonin by 55% (p<0.001), which was restored to control levels by olanzapine+melatonin. Body weight increased 18% in rats treated with olanzapine alone, but only 10% with olanzapine+melatonin, 5% with melatonin alone, and 7% with vehicle control. Body weight and visceral fat pad weight increases in rats treated with olanzapine alone were greater than in each of the other three groups (all p<0.01), which were not significantly different. These results suggest that olanzapine-induced increases in body weight and visceral adiposity may be at least in part secondary to olanzapine-induced reduction of plasma melatonin levels, and that melatonin may be useful for the management of olanzapine-induced weight gain in humans.
Insights
Melatonin may help manage olanzapine-induced weight gain. This study found that melatonin reversed weight and visceral fat increases in rats treated with olanzapine, an antipsychotic drug.
Area of Science:
- Pharmacology
- Endocrinology
- Neuroscience
Background:
- Atypical antipsychotics like olanzapine are associated with significant weight gain and visceral adiposity.
- Melatonin, a pineal hormone, has demonstrated efficacy in reversing age-related weight and fat accumulation in rodent models.
- The potential interaction between olanzapine and melatonin in regulating body weight remains largely unexplored.
Purpose of the Study:
- To investigate whether melatonin administration can counteract olanzapine-induced increases in body weight and visceral adiposity in a rat model.
- To explore the potential role of olanzapine's effect on endogenous melatonin levels in mediating these metabolic changes.
Main Methods:
- Female rats were administered olanzapine, melatonin, a combination of both, or vehicle control for eight weeks.
- Body weight, food and water intake, and locomotor activity were monitored throughout the study.
- Nocturnal plasma melatonin concentrations were measured, and visceral fat pads were weighed post-mortem.
Main Results:
- Olanzapine treatment significantly reduced nocturnal plasma melatonin levels by 55%.
- Olanzapine administration led to an 18% increase in body weight, which was attenuated to 10% when co-administered with melatonin.
- Both body weight and visceral fat pad weight increases were significantly greater in the olanzapine-only group compared to all other groups.
Conclusions:
- Olanzapine-induced weight gain and visceral adiposity may be partly mediated by a reduction in plasma melatonin levels.
- Melatonin administration shows potential as a therapeutic strategy to manage olanzapine-associated weight gain in humans.
- Further research is warranted to elucidate the precise mechanisms and clinical utility of melatonin in this context.
