Modulation of Taste-Related Behavior by Molecular Mediators of Appetite & Satiety

食欲分子介质对味觉相关行为的调节

• 批准号: 9091556
• 负责人: Steven D Munger
• 金额: $ 36.47万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-15 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9091556
• 关键词: Address; Adult; Affect; Animal Model; Behavior; Behavioral; Biology; Blood Circulation; Body Weight; Body Weight decreased; Cells; Clinical Trials; Collaborations; Data; Desire for food; Detection; Diabetes Mellitus; Diet; Disease; Dose; Eating; Endocrine; Endocrine System Diseases; Endocrine system; Family; Feeding behaviors; Florida; Food Energy; Genetic; Glucagon; Health; Homeostasis; Hormonal; Hormones; Human; Incidence; Institutes; Knock-out; Knockout Mice; Knowledge; Lead; Learning; Life Style; Link; Lipids; Mediating; Mediator of activation protein; Medical Research; Metabolic; Metabolic Diseases; Modality; Modeling; Molecular; Molecular Biology; Mus; Nutrient; Obese Mice; Obesity; Oral cavity; Peptide YY; Peptides; Perception; Peripheral; Pharmacology; Plague; Play; Protocols documentation; Recombinants; Regulation; Reporting; Research; Role; Saliva; Salivary; Salivary Glands; Satiation; Sensory; Signal Transduction; Societies; Stomach; Sweetening Agents; Taste Buds; Taste Perception; Taste aversion; Testing; Therapeutic Effect; Thinking; Time; Tissues; Transgenes; Transgenic Organisms; Universities; Viral; Wild Type Mouse; adeno-associated viral vector; base; blood glucose regulation; cell type; detection of nutrient; energy balance; gastric secretion substance; gene therapy; glucagon-like peptide; member; neuropeptide Y; novel; novel therapeutics; obesity treatment; paracrine; receptor; reconstitution; reduced food intake; response; sweet taste perception; taste stimuli; taste system; tongue papilla; vector

DESCRIPTION (provided by applicant): Two paradigm-shifting discoveries in taste research in recent years have realigned our thinking as to how taste perception is linked to mechanisms of appetite and satiety. The first was that many cells in the gut express the same molecular machinery required for nutrient detection as that found in taste cells. We now know these receptors in the gut detect ingested nutrients and mediate the secretion of gastric hormones. More recently, it was learned that these 'gastric' hormones together with their cognate receptors are also expressed in taste cells in the peripheral gustatory system. This latest discovery has raised a fundamental challenge to the field to understand how these peripheral 'gastric' hormones affect taste function and ingestive behavior. Given the worldwide rising incidence of diabetes, obesity and related metabolic disorders, we are proposing research that addresses our dearth of knowledge regarding the hormonal modulation of chemosensory perception and how disruption of hormonal signaling in the taste system can impact upon food intake and energy homeostasis. We have recently reported that the gut hormone, glucagon-like peptide 1 (GLP-1), can modulate sweet taste sensitivity. We have also reported that another GI peptide, glucagon, which plays a major role in the regulation of glucose homeostasis, can also act to modulate taste sensitivity to sweeteners. These results, when placed in the context of our preliminary findings on the hormone peptide YY (PYY) suggest that the gustatory system is indeed being dynamically modulated through hormonal action. The neuropeptide Y (NPY) family peptides, NPY and PYY, play a major role in the regulation of satiety when expressed by gut cells and/or in CNS tissues. Currently, PYY is being viewed as a candidate treatment for obesity and has been through clinical trials because of its ability to reduce food intake. However, unfortunately, high doses of PYY given systemically also cause conditioned taste aversion (CTA). Our data suggesting that PYY introduced into the oral cavity, while leading to significant weight loss in animal models, does not induce CTA, reintroduces PYY as a putative treatment for obesity. The presence of these NPY family peptides in the oral cavity, along with the expression of their cognate receptor(s) in gustatory tissues suggests that they may be influencing ingestive behavior by affecting the functioning of the peripheral gustatory system. Using a combination of genetic and pharmacological models, the proposed studies focus on investigating the general hypothesis that taste-related behavior can be modulated by metabolic hormones such as PYY and/or NPY.

描述（由申请人提供）：近年来味觉研究中的两个范式转变的发现重新调整了我们对味觉感知如何与食欲和饱腹感机制联系起来的思考。首先，肠道中的许多细胞表达的营养检测所需的分子机制与味觉细胞中的分子机制相同。我们现在知道肠道中的这些受体可以检测摄入的营养物质并介导胃激素的分泌。最近，人们了解到这些“胃”激素及其同源受体也在外周味觉系统的味觉细胞中表达。这一最新发现对该领域提出了根本性的挑战，即了解这些外周“胃”激素如何影响味觉功能和摄入行为。鉴于全球范围内糖尿病、肥胖症和相关代谢紊乱的发病率不断上升，我们正在提出一项研究，以解决我们对化学感觉感知的激素调节以及味觉系统中激素信号传导的破坏如何影响食物摄入和能量稳态方面缺乏了解的问题。 我们最近报道，肠道激素胰高血糖素样肽 1 (GLP-1) 可以调节甜味敏感性。我们还报道了另一种胃肠道肽胰高血糖素，它在调节葡萄糖稳态中起主要作用，也可以调节对甜味剂的味觉敏感性。当将这些结果置于我们对激素肽 YY (PYY) 的初步研究结果中时，表明味觉系统确实通过激素作用进行动态调节。 神经肽 Y (NPY) 家族肽 NPY 和 PYY 在肠道细胞和/或中枢神经系统组织中表达时，在饱腹感调节中发挥着重要作用。目前，PYY 被视为肥胖症的候选治疗方法，并且由于其能够减少食物摄入量而已经通过了临床试验。然而， 不幸的是，全身给予高剂量的 PYY 也会引起条件性味觉厌恶 (CTA)。我们的数据表明，将 PYY 引入口腔虽然会导致动物模型体重显着减轻，但不会诱导 CTA，从而重新将 PYY 引入肥胖症的推定治疗方法。这些 NPY 家族肽在口腔中的存在，以及其同源受体在味觉组织中的表达表明，它们可能通过影响外周味觉系统的功能来影响摄入行为。拟议的研究结合遗传和药理学模型，重点调查以下一般假设：味觉相关行为可以通过代谢激素（如 PYY 和/或 NPY）调节。