Niacin's effect on fatty acids and inflammatory markers (NEFA-IM)

烟酸对脂肪酸和炎症标志物的影响 (NEFA-IM)

• 批准号: 8100438
• 负责人: Richard Louis Dunbar
• 金额: $ 13.73万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 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 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8100438
• 关键词: Acute; Adipocytes; Adipose tissue; Atherosclerosis; Award; Biopsy Specimen; Blood Glucose; Carbohydrates; Cholesterol; Clinical; Clinical Trials; Collaborations; Complement; Data; Dermal; Dermis; Dose; Dyslipidemias; Environment; Fatty Acids; Fatty acid glycerol esters; Functional disorder; Funding; Future; Genetic Crossing Over; Glucose; Goals; Hepatic; High Density Lipoprotein Cholesterol; High Density Lipoproteins; Histology; Hour; Hyperemia; Hypertriglyceridemia; Immunohistochemistry; In Situ Hybridization; In Vitro; Indomethacin; Inflammation; Instruction; Insulin Resistance; Interleukin-6; Internist; Intravenous; Knowledge; Laser-Doppler Flowmetry; Lead; Leukocytes; Link; Lipids; Lipoproteins; Mediating; Mentors; Mentorship; Messenger RNA; Metabolic syndrome; Metabolism; Molecular; Myocardial Infarction; Nicotinic Acids; Nonesterified Fatty Acids; Nutrient; Nutritional; Oral; Outcome; Pathway interactions; Peripheral; Physiological; Placebos; Plasma; Prevention; Prostaglandin D2; Prostaglandins; Publications; Recording of previous events; Research Personnel; Research Project Grants; Resistance; Reverse Transcriptase Polymerase Chain Reaction; Role; Sample Size; Sampling; Science; Skin; Specialist; Specimen; Techniques; Temperature; Testing; Thermometry; Tissues; Training; Training Support; Translating; Translational Research; Triglycerides; Variant; Very low density lipoprotein; Work; abstracting; career; clinical effect; cytokine; fatty acid metabolism; improved; in vivo; indexing; inflammatory marker; inhibitor/antagonist; insulin sensitivity; intravenous glucose tolerance test; mRNA Expression; patient oriented research; pharmacodynamic model; prevent; programs; research study; response; skills; subcutaneous; sugar; tool; translational medicine; uptake

DESCRIPTION (provided by applicant): The candidate is a board-certified internist specializing in lipidology, starting a career in translational research focused on lipoprotein metabolism, its pathophysiology, and treatment. His short-term goal is mentored support to complete essential formal and practical training supporting his long-term goal, to develop into an independent academic investigator performing high-quality mechanistically-oriented patient-oriented research advancing lipid science and atherosclerosis prevention. Key skills are directed at probing mechanisms, including the use of pharmacologic and physiologic challenges and molecular techniques. The candidate will gain a working knowledge of the proper application of these skills and a publication record in their use, helping him to compete as an independent researcher. This training will enhance the clinical trials of the research project, and include two provocative nutrient challenges, pharmacodynamic modeling, and mRNA expression of clinical samples using in situ hybridization and RT-PCR. Specific hypotheses related to Niacin's Effects on Fatty Acids and Inflammatory Markers (NEFA-IM) are assessed using a niacin challenge to provoke acute changes in insulin sensitivity and postprandial lipidemia. The overall hypothesis is that free fatty acid rebound following niacin a) mediates niacin-induced insulin resistance, and b) interferes with postprandial triglyceride lowering and HDL raising. Hypotheses are tested .by suppressing the free fatty acid rebound with a prostaglandin synthesis inhibitor. Two clinical trials evaluate subjects with metabolic syndrome, a) during an intravenous glucose challenge, and b) an oral fat tolerance test. Complementary analyses include ex vivo analyses from clinical samples evaluated with molecular techniques, in collaboration with appropriate specialists. Advisors are established researchers with expertise related to the major aims, and a history of successful mentorship in an environment known for its emphasis on translational medicine of the kind proposed. This award will help the candidate develop needed skills and preliminary data to support an application for traditional funding that would translate promising findings into the clinical therapy setting. RELEVANCE (See instructions): Niacin is effective at treating high cholesterol and preventing heart attacks, but sometimes raises blood sugar. The purpose of this study is to test a technique that may prevent changes in sugar and even improve cholesterol lowering by niacin. If this is successful, it may lead to future strategies to improve niacin therapy. (End of Abstract)

描述（由申请人提供）：候选人是专门从事脂质学的董事会认证的国内学，从事转化研究的职业，重点是脂蛋白代谢，其病理生理学和治疗。他的短期目标是指导支持，以完成支持他的长期目标的基本正式和实践培训，以发展为独立的学术研究员，从事高质量的机械方向研究的研究，以患者为导向的研究推进了脂质科学和预防动脉粥样硬化。关键技能致力于探测机制，包括使用药理学和生理挑战和分子技术。候选人将获得有关这些技能的适当应用以及在使用中出版记录的工作知识，从而帮助他竞争独立的研究人员。该培训将增强研究项目的临床试验，包括两种挑衅性的营养挑战，药效学建模以及使用原位杂交和RT-PCR的临床样品的mRNA表达。使用烟酸挑战来评估与烟酸对脂肪酸和炎症标志物（NEFA-IM）的影响有关的特定假设，以促进胰岛素敏感性和餐后脂肪血症的急性变化。总体假设是，烟酸后的游离脂肪酸反弹a）介导烟酸诱导的胰岛素抵抗，b）干扰餐后甘油三酸酯降低和HDL升高。通过抑制前列腺素合成抑制剂来抑制游离脂肪酸的反弹，对假设进行了测试。两项临床试验评估了代谢综合征的受试者，a）在静脉葡萄糖挑战期间和b）口服脂肪耐受性测试。互补分析包括与适当专家合作评估的临床样本的实体分析。顾问是具有与主要目标有关的专业知识的成熟研究人员，并且在以这种环境中着重于转化医学而闻名的环境中成功指导的历史。该奖项将有助于候选人发展所需的技能和初步数据，以支持传统资金的应用程序，该申请将有希望的发现转化为临床治疗环境。相关性（请参阅说明）：烟酸可有效治疗高胆固醇和预防心脏病发作，但有时会增加血糖。这项研究的目的是测试一种可能防止糖变化甚至改善烟酸降低胆固醇的技术。如果这成功，它可能会导致未来改善烟酸疗法的策略。 （抽象的结尾）