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

应聘者描述(由应聘者提供)：应聘者是一名获得委员会认证的内科医生，专门从事脂蛋白代谢、其病理生理学和治疗方面的翻译研究。他的短期目标是在导师的支持下完成必要的正式和实践培训，以支持他的长期目标，发展成为一名独立的学术研究员，进行高质量的、以机械为导向的、以患者为导向的研究，促进血脂科学和动脉粥样硬化的预防。关键技能针对的是探测机制，包括使用药理学和生理学挑战以及分子技术。候选人将获得正确应用这些技能的实用知识和使用这些技能的出版记录，帮助他作为独立研究人员竞争。这次培训将加强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，以及使用原位杂交和RT-PCR对临床样本进行mRNA表达。与烟酸对脂肪酸和炎症标记物(NEFA-IM)的影响相关的特定假说通过烟酸激发胰岛素敏感性和餐后血脂的急性变化来评估。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)干扰餐后甘油三酯的降低和高密度脂蛋白的升高。通过用前列腺素合成抑制剂抑制游离脂肪酸反弹来检验假说。两项临床试验评估了代谢综合征受试者，a)静脉血糖挑战期间，b)口服脂肪耐量试验。补充分析包括与适当的专家合作，用分子技术评估临床样本的体外分析。顾问是具有与主要目标相关的专业知识的知名研究人员，以及在以强调所提议的那种转化医学而闻名的环境中成功指导的历史。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，将有希望的发现转化为临床治疗环境。相关性(参见说明)：烟酸在治疗高胆固醇和预防心脏病方面有效，但有时会升高血糖。这项研究的目的是测试一种技术，该技术可以防止血糖变化，甚至可以改善烟酸降低胆固醇的效果。如果这是成功的，它可能会导致未来改进烟酸疗法的策略。(摘要结束)

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)