Cope M B, Jumbo-Lucioni P, Walton R G, Kesterson R A, Allison D B, Nagy T R
Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL 35294-3360, USA.
Int J Obes (Lond). 2007 Jun;31(6):1014-22. doi: 10.1038/sj.ijo.0803533. Epub 2007 Jan 16.
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.
Test the hypothesis that the obesigenic effects of these drugs are greater in the presence of a high-fat diet.
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.
AAD-treated mice gained significantly more weight than controls after 3 weeks (P<0.001). Treatment and diet had significant effects on FI and EI over time (P<0.001). AAD-treated mice had significantly higher FE than controls (P<0.05); however, there was no significant drug by diet interaction (P=0.65). Risperidone low-fat mice gained significantly more absolute fat mass than placebo low-fat mice (P<0.05). All treatment groups, except quetiapine low-fat and olanzapine high-fat, gained significantly more absolute lean mass than placebo controls (P<0.05). Cholesterol levels were significantly lower in quetiapine and risperidone than placebo (P<0.05). Risperidone low-fat mice had significantly higher triglyceride levels than placebo and risperidone high-fat mice (P<0.05).
A high-fat diet does not increase AAD-induced BW gain in female mice during a 3-week treatment period.
非典型抗精神病药物（AAD）可使雌性C57BL/6J小鼠显著体重增加。在此模型中，饮食脂肪对体重增加和血脂的影响尚不清楚。
检验在高脂饮食情况下这些药物的致肥胖作用更强这一假设。
对雌性C57BL/6J小鼠用非典型抗精神病药物治疗3周，并给予低脂或高脂饮食（脂肪含量分别为4.6%和15.6%，按重量计）。在用优化剂量的奥氮平、喹硫平和利培酮治疗期间，测量食物摄入量（FI）、体重（BW）、身体组成和血脂。计算能量摄入量（EI）和饲料效率（FE）。通过重复测量方差分析（ANOVA）分析变化的组间差异。使用双向ANOVA比较血脂浓度、EI和FE。
3周后，接受AAD治疗的小鼠比对照组体重显著增加更多（P<0.001）。随着时间推移，治疗和饮食对FI和EI有显著影响（P<0.001）。接受AAD治疗的小鼠的FE显著高于对照组（P<0.05）；然而，饮食与药物之间没有显著的相互作用（P=0.65）。利培酮低脂组小鼠比安慰剂低脂组小鼠获得的绝对脂肪量显著更多（P<0.05）。除喹硫平低脂组和奥氮平高脂组外，所有治疗组比安慰剂对照组获得的绝对瘦体量显著更多（P<0.05）。喹硫平和利培酮组的胆固醇水平显著低于安慰剂组（P<0.05）。利培酮低脂组小鼠的甘油三酯水平显著高于安慰剂组和利培酮高脂组小鼠（P<0.05）。
在为期3周的治疗期内，高脂饮食不会增加雌性小鼠中AAD诱导的体重增加。
