Physiological mechanisms underlying alterations in diet preference

摘要 肥胖是包括高血压和II型糖尿病在内的慢性健康并发症的关键危险因素 糖尿病隔日禁食（ADF）涉及喂养和禁食的周期， 对减轻体重和改善人类和大鼠的代谢措施有效。我们有 最近报道，大鼠同时提供标准食物和高能量（HE）饮食， 几乎完全摄入HE饮食。然而，ADF范式的大鼠显示出减少的HE饮食， 食物摄入量增加导致的偏好。膳食模式分析提供参数， 作为膳食大小和数量，揭示了雄性和雌性大鼠在ADF时间表上的差异。餐 模式参数由生理信号驱动 刺激和进餐开始）和终止摄入（例如饱腹感）。在这里，男性和女性的ADF 和对照组大鼠进行比较，以研究1）味觉信号传导和2）肠肽的作用 影响，在ADF诱导的饮食偏好的变化。使用cFos免疫组织化学， 激活与味觉识别相关的中枢味觉通路中的脑区， 奖励将在各组之间进行比较（实验1）。这些实验旨在 测试ADF和对照喂养时间表的大鼠显示类似的激活的假设， 大脑区域参与味觉识别，但ADF大鼠显示神经激活减少 味觉通路参与奖赏的过程另一组雄性和雌性ADF大鼠和对照大鼠 将被用于（实验2）研究显示参与饱腹感的肠肽的作用 (CCK)以及饱腹感和奖赏（GLP-1）。各组将给予激动剂， CCK和GLP-1受体拮抗剂，以检验饮食偏好改变的假设 由ADF时间表诱导，减少了与奖励有关的肠道信号，但不是饱腹感。的 设计实验来评估膳食模式参数如何随着进食而改变 时间表和肠肽给药。从拟议的实验结果将 提供有关味觉和肠道信号驱动的神经机制的信息 饮食偏好的变化。

ABSTRACT Obesity is a key risk factor for chronic health complications including hypertension and Type II diabetes. Alternate day fasting (ADF) which involve cycles of feeding and fasting have been effective for weight loss and improving metabolic measures in humans and rats. We have recently reported that rats presented both standard chow and a high energy (HE) diet show almost exclusive intake of the HE diet. Yet, rats on an ADF paradigm show decreased HE diet preference driven by increased chow intake. Meal pattern analyses that provide parameters such as meal size and number, reveal differences in male and female rats on an ADF schedule. Meal pattern parameters are driven by physiological signals that drive intake (e.g. orosensory stimulation and meal initiation) and terminate intake (e.g. satiety). Here, male and female ADF and control rats will be compared to investigate the role of 1) taste signaling and 2) gut peptide influences, in ADF-induced shifts in diet preference. Using cFos immunohistochemistry, activation of brain areas in central gustatory pathways associated with taste identification and reward will be compared between the groups (Experiment 1). These experiments are designed to test the hypothesis that rats on ADF and control feeding schedules show similar activation of brain regions involved in taste identification but that ADF rats show decreased neural activation of taste pathways involved in reward. Another cohort of male and female ADF and control rats will be used (Experiment 2) to investigate the role of gut peptides shown to be involved in satiety (CCK) and both satiety and reward (GLP-1). Groups will be administered agonists and antagonists of CCK and GLP-1 receptors to test the hypothesis that shifts in diet preference induced by an ADF schedule, reduces gut signals related to reward but not satiety. The experiments are designed to assess how meal pattern parameters are altered with feeding schedule and gut peptide administration. The findings from the proposed experiments will provide information about how neural mechanisms related to taste and gut signaling drive changes in diet preference.