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

描述（由申请人提供）：该候选人是一名委员会认证的内科医生，专门从事脂质学，开始从事转化研究，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，以完成必要的正式和实践培训，支持他的长期目标，发展成为一个独立的学术研究者，进行高质量的以机械为导向的以患者为导向的研究，推进脂质科学和动脉粥样硬化预防。关键技能是针对探测机制，包括使用药理学和生理学的挑战和分子技术。候选人将获得正确应用这些技能的工作知识，并在其使用的出版记录，帮助他作为一个独立的研究人员竞争。该培训将加强该研究项目的临床试验，包括两个挑衅性的营养挑战，药效学建模和使用原位杂交和RT-PCR的临床样本的mRNA表达。与烟酸对脂肪酸和炎症标志物的影响（NEFA-IM）相关的特定假设使用烟酸激发引起胰岛素敏感性和餐后胰岛素敏感性的急性变化进行评估。总的假设是烟酸后游离脂肪酸反弹a）介导烟酸诱导的胰岛素抵抗，和B）干扰餐后甘油三酯降低和HDL升高。通过用前列腺素合成抑制剂抑制游离脂肪酸反弹来验证假设。两项临床试验评估了代谢综合征受试者，a）在静脉内葡萄糖激发期间，和B）口服脂肪耐量试验。补充分析包括与适当的专家合作，对使用分子技术评价的临床样品进行离体分析。顾问是建立研究人员与专业知识相关的主要目标，并在一个环境中成功的指导历史，其重点是转化医学的那种建议。该奖项将帮助候选人发展所需的技能和初步数据，以支持传统资金的申请，将有前途的发现转化为临床治疗环境。相关性（见说明书）：烟酸对治疗高胆固醇和预防心脏病发作有效，但有时会升高血糖。这项研究的目的是测试一种技术，可以防止糖的变化，甚至提高烟酸降低胆固醇。如果这是成功的，它可能会导致未来的战略，以改善烟酸治疗。 (End摘要）

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)