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他莫昔芬和/或雌二醇对去卵巢大鼠摄食行为、美味食物和代谢参数的慢性给药作用。

Effect of chronic administration of tamoxifen and/or estradiol on feeding behavior, palatable food and metabolic parameters in ovariectomized rats.

机构信息

Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde - ICBS, UFRGS (Saúde), RS, Brazil.

出版信息

Physiol Behav. 2013 Jul 2;119:17-24. doi: 10.1016/j.physbeh.2013.05.026. Epub 2013 May 17.

Abstract

Tamoxifen (TAM) is a selective estrogen receptor modulator (SERM) used in the treatment of breast cancer; however many women complain of weight gain during TAM treatment. The anorectic effects of estradiol (E) and TAM are well known, although the effects of E on the consumption of palatable food are controversial and there is no information regarding the effects of TAM on palatable food consumption. The aim of this study was to investigate the effects of chronic treatment with estradiol and/or tamoxifen on feeding behavior in ovariectomized rats exposed to standard chow and palatable foods (Froot Loops® or chocolate). Additionally, parameters such as body weight, uterine weight, lipid profile and plasma glucose were also measured. Wistar rats were ovariectomized (OVX) and subsequently injected (ip.) for 40 days with: E, TAM, E+TAM or vehicle (OVX and SHAM - controls). Behavioral tests were initiated 25 days after the start of treatment. Froot Loops® consumption was evaluated in a novel environment for 3 min. Standard chow intake was evaluated for two days and chocolate intake for 7 days in the home cage in a free choice model (chocolate or standard chow). Rats injected with E, TAM and E+TAM groups showed a reduction in body weight and standard chow intake, compared with control groups. With regard to palatable food intake, the E, TAM and E+TAM groups demonstrated increased consumption of Froot Loops®, compared with the SHAM and OVX groups. In contrast, all groups increased their consumption of chocolate, compared with standard chow; however the E group consumed more chocolate than the OVX, TAM and E+TAM groups. Despite these differences in chocolate consumption, all groups showed the same caloric intake during the chocolate exposure period; however the TAM and E+TAM groups presented decreased body weight. Treatment with estradiol and tamoxifen showed a favorable lipid profile with low levels of TC, LDL, LDL/HDL ratio and lower levels of plasma glucose. The E group presented high levels of TG and HDL, when compared with the TAM and E+TAM groups. Taken together, results suggest that TAM acted in an estrogen-like manner on the majority of parameters analyzed. However, tamoxifen acts in a different manner depending on the type of palatable food and the exposure. In addition, the TAM group demonstrated weight loss, compared with other groups independently of the type of food presented (palatable food or standard chow), showing a low caloric efficiency.

摘要

他莫昔芬(TAM)是一种选择性雌激素受体调节剂(SERM),用于治疗乳腺癌;然而,许多女性在接受 TAM 治疗时会抱怨体重增加。众所周知,雌二醇(E)和 TAM 具有厌食作用,尽管 E 对美味食物的消耗作用存在争议,并且没有关于 TAM 对美味食物消耗作用的信息。本研究旨在研究长期给予雌二醇和/或他莫昔芬对暴露于标准食物和美味食物(Froot Loops®或巧克力)的去卵巢大鼠摄食行为的影响。此外,还测量了体重、子宫重量、血脂谱和血浆葡萄糖等参数。Wistar 大鼠接受卵巢切除术(OVX),随后连续 40 天通过腹腔注射(ip.)给予:E、TAM、E+TAM 或载体(OVX 和 SHAM-对照组)。治疗开始后第 25 天开始进行行为测试。在新环境中评估 3 分钟的 Froot Loops®摄入量。在自由选择模型中,在两天内评估标准食物摄入量,在 7 天内评估巧克力摄入量(巧克力或标准食物)。与对照组相比,接受 E、TAM 和 E+TAM 治疗的大鼠体重和标准食物摄入量均减少。关于美味食物的摄入量,E、TAM 和 E+TAM 组与 SHAM 和 OVX 组相比,Froot Loops®的摄入量增加。相比之下,所有组与标准食物相比,巧克力的摄入量均增加;然而,E 组比 OVX、TAM 和 E+TAM 组消耗更多的巧克力。尽管巧克力的摄入量存在差异,但所有组在巧克力暴露期间的热量摄入相同;然而,TAM 和 E+TAM 组体重减轻。雌二醇和他莫昔芬治疗表现出有利的血脂谱,TC、LDL、LDL/HDL 比值低,血浆葡萄糖水平低。与 TAM 和 E+TAM 组相比,E 组 TG 和 HDL 水平较高。综上所述,结果表明,TAM 对大多数分析参数表现出类似雌激素的作用。然而,他莫昔芬的作用方式取决于美味食物的类型和暴露方式。此外,与其他组相比,TAM 组表现出体重减轻,而与所呈现的食物类型(美味食物或标准食物)无关,表明热量效率低。

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