Physiological mechanisms underlying alterations in diet preference

摘要 肥胖是包括高血压和II型在内的慢性健康并发症的关键风险因素 糖尿病。隔日禁食(ADF)包括进食和禁食的循环 对人类和大鼠的减肥和改善新陈代谢措施有效。我们有 最近有报道称，大鼠既有标准饮食，也有高能饮食 几乎是独家摄取的HE饮食。然而，在ADF范例中的大鼠表现出减少了HE饮食 偏爱是由食物摄入量增加所驱动的。膳食模式分析提供了以下参数 如进食的大小和数量，显示在ADF时间表上的雄性和雌性大鼠的差异。大餐 模式参数由驱动摄取的生理信号(例如，口感)驱动 刺激和开始进餐)和终止摄取(例如饱腹感)。在这里，男性和女性ADF 与对照大鼠进行比较，以研究1)味觉信号和2)肠肽的作用 在ADF诱导的饮食偏好改变中的影响。使用CFOS免疫组织化学方法， 中枢味觉通路中大脑区域的激活与味觉识别和 奖励将在两组之间进行比较(实验1)。这些实验旨在 测试ADF和对照喂养计划的大鼠表现出类似的激活的假设 参与味觉识别的脑区，但ADF大鼠表现出神经激活减少 与奖赏有关的味觉通路。另一组雄性和雌性ADF和对照组大鼠 将被用来研究肠肽在饱腹感中的作用(实验2) (CCK)和满足感和奖赏(GLP-1)。各组将被给予激动剂和 CCK和GLP-1受体的拮抗剂来验证饮食偏好改变的假设 由ADF时间表诱导，减少与奖励有关的肠道信号，而不是满足感。这个 实验旨在评估进食模式参数是如何随着进食而改变的 时间表和肠肽给药。拟议中的实验结果将 提供与味觉和肠道信号相关的神经机制如何驱动的信息 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.