MECHANISMS OF PERIPHERAL FAT DETECTION

周围脂肪检测机制

• 批准号: 7924065
• 负责人: TIMOTHY A. GILBERTSON
• 金额: $ 34.68万
• 依托单位: UTAH STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7924065
• 关键词: Address; Anterior; Behavior; Behavioral Assay; Biological; Biological Assay; CD36 Antigens; CD36 gene; Cardiovascular Diseases; Cells; Cues; Data; Detection; Development; Diabetes Mellitus; Diet; Dietary Fats; Disease; Eating; End stage renal failure; Epidemic; Exercise; Fat Substitutes; Fatty Acids; Fatty acid glycerol esters; G-Protein-Coupled Receptors; Gene Expression; Genes; Goals; Inbred Strain; Inbred Strains Mice; Incidence; Indium; Individual; Intake; Investigation; Ion Channel; Laboratories; Lead; Link; Measures; Molecular; Molecular Biology; Mus; Nonesterified Fatty Acids; Nutrient; Nutritional; Nutritional status; Obesity; Oral cavity; Pathway interactions; Performance; Peripheral; Polyunsaturated Fatty Acids; Population; Potassium Channel; Property; Rattus; Receptor Cell; Regimen; Regulation; Research; Resistance; Rodent; Series; Signal Pathway; System; Taste Perception; Testing; Texture; Tissues; Tongue; base; experience; feeding; interdisciplinary approach; multidisciplinary; novel; nutrition; preference; receptor; receptor expression; receptor function; research study; response; somatosensory

The incidence of obesity worldwide continues to escalate with the spread of the Western diet and with it there has been a corresponding increase in cardiovascular disease, diabetes, end-stage renal disease and other obesity-related disorders. Of all the causes for obesity, the predominant one seems to be choice - the choice to eat more and exercise less. One of the choices that has been linked with obesity has been the selection of a high fat, calorically dense diet. Despite much research on the link between fat intake and obesity, relatively little is known about the chemosensory mechanisms that underlie the taste of fat and how these mechanisms might contribute to dietary fat intake. Our previous research has identified differences in how the taste systems in obesity-prone and –resistant rodents respond to fatty acids, a cue for dietary fat, and how this was correlated to differences in gene expression and receptor function. Moreover, we have demonstrated that these chemosensory mechanisms are modulated by diet and the development of obesity. The revised proposal focuses on pursuing a more focused, single remaining specific aim that seek to explore how the gustatory response to fat is modulated by dietary experience. There is new and emerging data that argues to the plasticity of the peripheral taste system, yet our understanding of how the system changes in relation to experience is poor at best. Specifically, we will use an approach including a multidisciplinary approach to answer the following question: 1. Is the fatty acid transduction pathway modulated by diet? Our multidisciplinary approach analyzing genes through behavior will be used to test the hypothesis that fat receptor expression in taste cells is altered during high fat feeding in a manner that results in an increased responsiveness to fatty acids. Following high fat dietary regimens, molecular, cell-based and behavioral assays will be performed to measure changes in four primary receptive elements in the fatty acid signaling pathway, including CD36, GPR 120, GPR 84 and fatty acid-sensitive DRK channels. Our extensive preliminary data generated in the previous period would argue that these are the primary components of the pathway that underlies the ability of the gustatory system to recognize and respond to free fatty acids.

随着西方饮食的传播，全世界肥胖的事件继续升级，随之而来的是心血管疾病，糖尿病，终末期肾脏疾病和其他与肥胖有关的疾病的相应增加。在肥胖的所有原因中，主要的选择似乎是选择 - 选择更多和锻炼的选择。与肥胖相关的选择之一是选择高脂，热量致密的饮食。尽管对脂肪摄入与肥胖之间的联系进行了大量研究，但对脂肪口味以及这些机制如何有助于饮食脂肪摄入的化学感应机制的了解相对较少。我们以前的研究已经确定了在容易肥胖和耐药啮齿动物中对脂肪酸的反应，饮食脂肪的提示以及这与基因表达和受体功能差异的相关性的差异。此外，我们已经证明了这些化学感应机制是通过饮食和物体发展来调节的。修订后的提案着重于追求更集中的，剩下的特定目标，该目标试图探讨饮食经验如何调节对脂肪的味觉反应。有关于周围味觉系统可塑性的新的和新兴的数据，但是我们对系统如何在体验中变化的理解充其量是很差的。具体来说，我们将使用一种方法，包括多学科方法来回答以下问题： 1。脂肪酸转移途径是否由饮食调节？我们通过行为的多学科方法分析仪基因将用于检验以下假设：在高脂肪进食过程中，味道细胞中的脂肪受体表达以增加对脂肪酸的反应性的方式改变。遵循高脂肪饮食方案，将进行分子，基于细胞和行为测定，以测量脂肪酸信号通路中四个主要受体元素的变化，包括CD36，GPR 120，GPR 84和脂肪酸敏感的DRK通道。我们上一个时期生成的广泛初步数据认为，这些是途径的主要组成部分，它是味道系统识别和响应游离脂肪酸的能力的基础。

项目成果

High-Fat Diet Alters the Orosensory Sensitivity to Fatty Acids in Obesity-Resistant but not Obesity-Prone Rats.

高脂肪饮食改变了抗肥胖大鼠但不改变肥胖倾向大鼠对脂肪酸的口腔感觉敏感性。

• DOI: 10.4172/1747-0862.1000168
• 发表时间: 2015
• 期刊: Journal of molecular and genetic medicine : an international journal of biomedical research
• 作者: Pittman,DavidW;Hansen,DaneR;Gilbertson,TimothyA
• 通讯作者: Gilbertson,TimothyA

Transient receptor potential channel type M5 is essential for fat taste.

• DOI: 10.1523/jneurosci.6273-10.2011
• 发表时间: 2011-06-08
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Liu P;Shah BP;Croasdell S;Gilbertson TA
• 通讯作者: Gilbertson TA

TRPM5 is critical for linoleic acid-induced CCK secretion from the enteroendocrine cell line, STC-1.

• DOI: 10.1152/ajpcell.00209.2011
• 发表时间: 2012
• 期刊: American journal of physiology. Cell physiology
• 作者: B. Shah;Pin Liu;Tian Yu;D. R. Hansen;T. Gilbertson

Activation of oral trigeminal neurons by fatty acids is dependent upon intracellular calcium.

• DOI: 10.1007/s00424-012-1116-9
• 发表时间: 2012-08
• 期刊: PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
• 影响因子: 4.5
• 作者: Yu, Tian;Shah, Bhavik P.;Hansen, Dane R.;Park-York, MieJung;Gilbertson, Timothy A.
• 通讯作者: Gilbertson, Timothy A.

Effects of poly-(lactide-co-glycolide) nanoparticles on electrophysiological properties of enteroendocrine cells.

• DOI: 10.1166/jnn.2011.3802
• 发表时间: 2011-04
• 期刊: Journal of nanoscience and nanotechnology
• 作者: B. Shah;S. Kona;T. Gilbertson;K. Nguyen