No effect of dietary fat on short-term weight gain in mice treated with atypical antipsychotic drugs

Abstract

Rationale: Atypical antipsychotic drugs (AAD) induce significant weight gain in female C57BL/6J mice. The effect of dietary fat on weight gain and serum lipids in this model is unknown. Objectives: Test the hypothesis that the obesigenic effects of these drugs are greater in the presence of a high-fat diet. Methods: Female C57BL/6J mice were treated with atypical antipsychotics for 3 weeks and fed either a low-fat or high-fat diet (4.6 vs 15.6% fat by wt). Food intake (FI), body weight (BW), body composition, and serum lipids were measured during treatment with optimized doses of olanzapine, quetiapine, and risperidone. Energy intake (EI) and feed efficiency (FE) were calculated. Group differences in change were analyzed via repeated measures analysis of variance (ANOVA). Serum lipid concentrations, EI and FE were compared using two-way ANOVA. Results: AAD-treated mice gained significantly more weight than controls after 3 weeks (Po0.001). Treatment and diet had significant effects on FI and EI over time (Po0.001). AAD-treated mice had significantly higher FE than controls (Po0.05); however, there was no significant drug by diet interaction (P ¼ 0.65). Risperidone low-fat mice gained significantly more absolute fat mass than placebo low-fat mice (Po0.05). All treatment groups, except quetiapine low-fat and olanzapine high-fat, gained significantly more absolute lean mass than placebo controls (Po0.05). Cholesterol levels were significantly lower in quetiapine and risperidone than placebo (Po0.05). Risperidone low-fat mice had significantly higher triglyceride levels than placebo and risperidone high-fat mice (Po0.05). Conclusions: A high-fat diet does not increase AAD-induced BW gain in female mice during a 3-week treatment period.

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

“…Similar results were observed in female Wistar rats, hooded-Lister rats, and CD-1 mice (2,3,12). However, our previous study in mice found olanzapine and risperidone induced a significant increase in lean mass, but not fat mass (22). The potential explanation was based on the age of the mice, as overfeeding young animals leads to an increase of lean mass, accounting for 80% of weight gain relative to adults, whose lean mass comprised only 15-30% of weight gain (22,25,26).…”

“…However, our previous study in mice found olanzapine and risperidone induced a significant increase in lean mass, but not fat mass . The potential explanation was based on the age of the mice, as overfeeding young animals leads to an increase of lean mass, accounting for 80% of weight gain relative to adults, whose lean mass comprised only 15‐30% of weight gain . Additionally, the increase in lean mass may be because of increases in insulin‐like growth factor 1 and Akt, both of which are increased by risperidone .…”

“…Animals were group housed for 1 week and then housed individually. Ten‐week‐old mice were acclimated to plain peanut butter pill administration (placebo; twice a day; 09:00 and 15:00 hours) for 2 weeks . After 2 weeks, mice were weighed, matched for body weight, and assigned to one of two groups ( n = 12/group), risperidone (RISP), or placebo (PLA).…”

“…Eight-week-old female C57BL/6J mice (Jackson Laboratory, Bar Harbor, ME, USA) were maintained on a 12/12 hour light/dark cycle (lights on at 6:00 hours) at 22.0 6 1.0 C. Animals were group housed for 1 week and then housed individually. Ten-week-old mice were acclimated to plain peanut butter pill administration (placebo; twice a day; 09:00 and 15:00 hours) for 2 weeks (4,22). After 2 weeks, mice were weighed, matched for body weight, and assigned to one of two groups (n ¼ 12/group), risperidone (RISP), or placebo (PLA).…”

Atypical antipsychotics and effects on feeding: from mice to men

“…In contrast to OLA studies in rodents, it is less clear whether sex effects can alter food intake and body weight with RIS or QUE administration. In female rodents, RIS has been associated with increased food intake and body weight (Baptista et al 2002;Cope et al 2007;Cope et al 2009;Kaur and Kulkarni 2002;Lian et al 2015;Ota et al 2002), although not all studies have shown a positive association (Fell et al 2007;Fell et al 2008;Hartfield et al 2006). Interestingly, a recent study suggested that female mice treated over 4 weeks with RIS-containing peanut butter pills gained weight but did not exhibit increased food intake, in contrast to concomitant hyperphagia with weight gain in animals treated with OLA or QUE (Cope et al 2007).…”