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Resistance to excessive bodyweight gain in risperidone-injected rats
Miyuki Ota1, Keiji Mori, Akira Nakashima
1Department of Neuropsychiatry, Tosei General Hospital, Seto, Japan.
Clinical and Experimental Pharmacology & Physiology
|April 7, 2005
Summary
Risperidone treatment in rats led to increased body weight despite reduced fat storage. This atypical antipsychotic drug altered white adipose tissue gene expression, promoting heat production and lipid mobilization.
Area of Science:
- Pharmacology and Toxicology
- Metabolic Research
- Endocrinology
Background:
- Atypical antipsychotics, like risperidone, are associated with metabolic side effects, including weight gain.
- The mechanisms underlying risperidone-induced weight gain, particularly concerning energy expenditure and lipid metabolism, require further elucidation.
- Understanding these mechanisms is crucial for managing the adverse effects of antipsychotic medications.
Purpose of the Study:
- To investigate the effects of chronic risperidone administration on body weight, body temperature, and lipid metabolism in rats.
- To explore the molecular changes in adipose tissue and other metabolic tissues in response to risperidone.
- To elucidate the potential mechanisms by which risperidone influences thermogenesis and lipid handling.
Main Methods:
- Rats were administered subcutaneous injections of risperidone (0.01 or 0.1 mg/kg/day) or vehicle for 21 consecutive days.
- Body weight and rectal temperature were monitored throughout the study.
- Serum levels of lipids, ketones, and thyroid hormones were measured; mRNA expression of genes involved in heat production and lipid metabolism in adipose tissue, skeletal muscle, and liver was analyzed using quantitative real-time PCR.
Main Results:
- Risperidone administration at 0.1 mg/kg/day resulted in significantly lower serum nonesterified fatty acid levels and a tendency for decreased serum beta-hydroxybutyrate.
- Chronic risperidone treatment upregulated mRNA expression of uncoupling protein 3, PPARgamma coactivator 1alpha, and PPARalpha in white adipose tissue.
- Expressions of lipogenic enzymes, hormone-sensitive lipase, and beta1-adrenoceptor were also enhanced in white adipose tissue.
Conclusions:
- Risperidone treatment appears to enhance the capacity for heat generation and lipid mobilization in white adipose tissue.
- These molecular adaptations in adipose tissue may contribute to reduced lipid storage and altered energy balance, potentially explaining the observed weight gain despite increased diet intake.
- The findings suggest a complex interplay between risperidone, thermogenesis, and lipid metabolism that warrants further investigation.