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移发现使我们对味觉感知如何与食欲和饱腹感相关的思考。首先是，肠道中的许多细胞表达了与味道细胞相同的营养检测所需的分子机械。现在，我们知道肠道中的这些受体检测摄入的营养素并介导胃激素的分泌。最近，据了解，这些“胃”激素以及它们的同源受体也在外周味系统的味道细胞中表达。这一最新发现提出了对该领域的根本挑战，以了解这些外围“胃”激素如何影响味觉功能和摄取行为。鉴于糖尿病，肥胖和相关代谢障碍的全球发病率上升，我们提出的研究涉及我们对化学感知荷尔蒙调节的知识的缺乏，以及味觉系统中激素信号传导如何影响食品摄入量和能量稳态。 我们最近报告说，肠激素，胰高血糖素样肽1（GLP-1）可以调节甜味味道敏感性。我们还报道说，在调节葡萄糖稳态中起主要作用的另一种GI肽胰高血糖素也可以调节对甜味剂的味觉敏感性。当将这些结果放置在我们对激素肽YY（PYY）的初步发现的背景下，表明味觉系统确实通过激素作用动态调节。 NPY和PYY的神经肽Y（NPY）家族肽在由肠道细胞和/或CNS组织中表达时在调节饱腹感中起主要作用。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的能力而进行了临床试验。然而， 不幸的是，高剂量的PYY在系统上也会引起条件味觉厌恶（CTA）。我们的数据表明，PYY引入了口腔，同时导致动物模型的大量体重减轻并不会引起CTA，而是重新引入PYY作为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系统的功能来影响摄取行为。拟议的研究通过结合遗传学模型，重点是研究与味觉相关的行为可以通过PYY和/或NPY等代谢激素调节的一般假设。