Department of Psychology, California State University Long Beach, Long Beach CA 90840, USA.
Department of Psychology, California State University Long Beach, Long Beach CA 90840, USA.
Neurosci Lett. 2023 Jun 21;808:137275. doi: 10.1016/j.neulet.2023.137275. Epub 2023 Apr 26.
Alternate day fasting (ADF) which involves the repetition of a 2-day cycle of a day of free access to food followed by a day of limited or no access to food, is an effective dietary intervention for weight loss in both humans and rats. We have previously reported that when presented with a high energy (HE) and standard chow diet, rats maintained on an ADF schedule displayed decreased HE diet preference compared to controls. Both male and female ADF rats increased overall intake of chow. However, this increase was driven by both meal size and meal number for males and only number of meals for females. Administration of cholecystokinin (CCK) or the glucagon-like peptide 1 (GLP-1) receptor agonist Exendin-4 (Ex-4) reduces food intake. It appears that CCK decreases food intake primarily through satiety signals whereas GLP-1 signaling may reduce intake by satiety and reward cues. Here, female and male rats were administered (i.p.) saline, 3.0 µg/kg Ex-4 (3 h before test), 3.0 µg/kg CCK (15 min before test) or a combination of both. Next, all rats were presented 23-h access to both HE diet and chow following food-restriction (ADF) or free access to chow (CON). Compared to saline-control sessions, administration of the combination of Ex-4 and CCK, but not Ex-4 or CCK alone, resulted in a decrease in both HE and chow intake early in the session for male ADF rats but the combination primarily decreased chow diet intake early in the session for female ADF rats. Thus, it appears that under these energy homeostatic conditions, administration of Ex-4 or CCK alone does not affect intake in ADF rats, but the combination produces decreases in feeding that are more than the sum of their individual effects. These findings support a role for the combination of GLP-1 and CCK signaling in the changes in diet preference induced by an alternate day fasting paradigm differentially in female and male rats.
隔日禁食（ADF）涉及重复进行 2 天周期，即在 1 天内自由进食，然后 1 天内限制或禁止进食，这是一种在人类和大鼠中有效控制体重的饮食干预方法。我们之前报道过，当大鼠摄入高热量（HE）和标准食物时，与对照组相比，按照 ADF 时间表进食的大鼠对 HE 饮食的偏好降低。雄性和雌性 ADF 大鼠的总进食量均增加。然而，这种增加是由雄性大鼠的每餐大小和餐数以及雌性大鼠的餐数驱动的。胆囊收缩素（CCK）或胰高血糖素样肽 1（GLP-1）受体激动剂 Exendin-4（Ex-4）的给药可以减少食物摄入。CCK 似乎主要通过饱腹感信号来减少食物摄入，而 GLP-1 信号可能通过饱腹感和奖励线索来减少摄入。在这里，雌性和雄性大鼠分别接受（ip）生理盐水、3.0µg/kg Ex-4（测试前 3 小时）、3.0µg/kg CCK（测试前 15 分钟）或两者的组合。然后，所有大鼠在限制食物（ADF）或自由进食（CON）后，都有 23 小时的时间可以接触到 HE 饮食和标准食物。与生理盐水对照组相比，仅 Ex-4 或 CCK 或 Ex-4 和 CCK 的组合给药可使雄性 ADF 大鼠在测试早期的 HE 和标准食物摄入量均减少，但组合主要使雌性 ADF 大鼠在测试早期减少标准食物的摄入量。因此，在这些能量稳态条件下，单独给予 Ex-4 或 CCK 并不影响 ADF 大鼠的摄食量，但组合会产生比其单独作用更大的摄食减少。这些发现支持了 GLP-1 和 CCK 信号的组合在 ADF 大鼠的饮食偏好改变中的作用，在雄性和雌性大鼠中，这种作用是不同的。
