Effects of risperidone on energy balance in female C57BL/6J mice

Abstract

Objective To investigate the effect of risperidone on energy expenditure and weight gain in female C57BL/6J mice. Design and Methods Body weight and composition, food intake, energy expenditure, and activity were determined weekly. mRNA expression of uncoupling protein 1 in brown adipose tissue, orexin and brain-derived neurotrophic factor in the hypothalamus were quantified by Real-Time PCR. Results Risperidone tended to induce a greater body weight gain (P=0.052) and significantly higher food intake (P=0.038) relative to the placebo-treated group. Risperidone-treated mice had a higher resting energy expenditure (P=0.001), and total energy expenditure (P=0.005) than the placebo group. There were no effects of treatment, time, and treatment by time on NREE between groups. Risperidone-treated mice showed a significantly lesser locomotor activity than placebo-treated mice over 3 weeks (P<0.001). Risperidone induced a higher UCP1 mRNA (P=0.003) and a lower orexin mRNA (P=0.001) than placebo. Discussion Risperidone-induced weight gain is associated with hyperphagia and a reduction in locomotor activity in C57BL/6J mice. Additionally, higher total and resting energy expenditure were accompanied by higher levels of UCP1 mRNA in BAT. The increased total energy expenditure could not offset the total intake of energy through risperidone-induced hyperphagia, therefore resulting in weight gain in female C57BL/6J mice.

Propranolol Attenuates Risperidone-Induced Trabecular Bone Loss in Female Mice

“…This was in addition to hyperphagia and weight gain. Recently, Li et al (48) showed that resting EE was higher in similarly dosed mice. Similar to our finding of reduced wheel activity (Figure 2), the authors found fewer x,y beam breaks over their 3-week study and elevated Ucp1 expression in the BAT of their mice (48).…”

“…Recently, Li et al (48) showed that resting EE was higher in similarly dosed mice. Similar to our finding of reduced wheel activity (Figure 2), the authors found fewer x,y beam breaks over their 3-week study and elevated Ucp1 expression in the BAT of their mice (48). We did not observe weight gain or hyperphagia in our mice, which could in part be due to the lower dose used in our study (0.75 mg/kg once daily by oral gavage) compared to that above (47,48).…”

The effect of antidepressants and antipsychotics on weight gain in children and adolescents

“…Mechanisms for this weight gain are unclear. Despite the weight gain effect being widely presumed to be related to hyperphagia , other animal studies have also shown that a transient increase in appetite is accompanied by decreased energy expenditure and decreased thermogenic activity in brown adipose tissue . Interestingly, McCracken et al .…”

Characterization of risperidone-induced weight gain mediated by alterations of the gut microbiome and suppression of host energy expenditure

“…Nine weeks of risperidone treatment led to a 2.5 g increase in body weight (Figure 3-6A, p < 0.05). Food intake behavior for C57BL/6J mice was found to be similar between groups, resulting in normal daily caloric ingestion, as reported previously for risperidone (Figure 3-6B) [215][216][217][218] . Similarly, risperidone treatment had no effect on digestive efficiency (Figure 3-6C).…”

“…However, the undoubetly multifactorial nature of the cardiometabolic effects is not completely understood, and patients still suffer from the side effects of weight gain. In humans, risperidone may promote weight gain through appetite stimulation, although many animal studies comparing SGAs challenge this hypothesis [215][216][217][218] . Risperidone-induced weight gain is believed to be multifaceted, involving genetic, metabolic, and environmental contributors 219,220 .…”