Sex and estrogens alter the action of glucagon-like peptide-1 on reward.
Sex and estrogens alter the action of glucagon-like peptide-1 on reward.
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DOI：
10.1186/s13293-016-0059-9
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发表时间：
2016
影响因子：
7.9
通讯作者：
Skibicka KP
中科院分区：
文献类型：
--
作者：
Richard JE;Anderberg RH;López-Ferreras L;Olandersson K;Skibicka KP
摄食行为是通过一系列复杂的厌食和厌氧激素作用于中枢神经系统（CNS）来调节的。其中一些激素对男性和女性可能有不同的作用，这种作用可能归因于性腺类固醇，尤其是雌激素的作用。中枢刺激胰高血糖素样肽-1 （GLP-1）受体通过作用于对雌激素的厌食作用重要的中枢神经系统区域，减少摄食和食物奖励行为。因此，我们提出GLP-1对食物摄入和奖励的作用可能因性别而异。在非剥夺或食物限制状态下，雄性和雌性大鼠中央注射GLP-1类似物exendin-4 (Ex4)；奖励行为在递进比操作条件反射任务中被测量。还测量了食物和美味食物的摄入量。为了确定Ex4作用的性别差异是否与雌激素相互作用有关，在Ex4治疗之前，先用非选择性雌激素受体-α (ERα)和ERβ或ERα选择性拮抗剂治疗。中枢注射Ex4显示，在操作性条件反射任务中，与男性相比，女性的奖励行为抑制增加。这种增加在未被剥夺食物和限制食物的动物中都存在，在喂食状态下差异更大。在Ex4之后，男性和女性的食物和美味食物的摄入量是相似的。经ER拮抗剂预处理后，Ex4的作用在两性中均被食物奖励而非食物摄入减弱，提示雌激素可能调节Ex4在两性中的作用。此外，er α-选择性拮抗剂中央预处理足以减弱Ex4对奖赏的影响。总的来说，这些数据表明雌性对中央GLP-1受体激活的食物奖励影响表现出更高的敏感性。令人惊讶的是，他们还证明了中枢ERα信号对于GLP-1在两性食物奖励行为中的作用是必要的。
Feeding behavior is regulated through an intricate array of anorexic and orexigenic hormones acting on the central nervous system (CNS). Some of these hormones may have differential effects in males and females, effects potentially attributed to actions of gonadal steroids, especially estrogens. Central stimulation of the glucagon-like peptide-1 (GLP-1) receptors reduces feeding and food-reward behavior by acting on CNS regions important for the anorexic actions of estrogens. Thus, we propose that the action of GLP-1 on food intake and reward may differ between sexes. Male and female rats were centrally injected with the GLP-1 analog exendin-4 (Ex4) in a non-deprived or food-restricted state; reward behavior was measured in a progressive ratio operant conditioning task. Intake of chow and palatable food were also measured. To determine if sex differences in the actions of Ex4 are due to interactions with estrogens, Ex4 treatment was preceded by treatment with a nonselective estrogen receptor-α (ERα) and ERβ or ERα-selective antagonist. Central injection of Ex4 revealed increased reward behavior suppression in females, compared to males, in the operant conditioning task. This increase was present in both non-deprived and food-restricted animals with larger differences in the fed state. Intake of chow and palatable food, after Ex4, were similar in males and females. Food reward, but not food intake, effect of Ex4 was attenuated by pretreatment with ER antagonist in both sexes, suggesting that estrogens may modulate effects of Ex4 in both sexes. Furthermore, central pretreatment with ERα-selective antagonist was sufficient to attenuate effects of Ex4 on reward. Collectively, these data reveal that females display much higher sensitivity to the food reward impact of central GLP-1 receptor activation. Surprisingly, they also demonstrate that central ERα signaling is necessary for the actions of GLP-1 on food-reward behavior in both sexes.