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: 8269045
• 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 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8269045
• 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）：该候选人是一名委员会认证的专攻脂质学的内科医生，开始了脂蛋白代谢、病理生理学和治疗方面的转化研究。他的短期目标是指导支持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。该培训将加强研究项目的临床试验，包括两个具有挑衅性的营养挑战，药效学建模，以及使用原位杂交和RT-PCR的临床样品mRNA表达。使用烟酸刺激引起胰岛素敏感性和餐后血脂的急性变化，评估了与烟酸对脂肪酸和炎症标志物（NEFA-IM）影响相关的特定假设。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，b)干扰餐后甘油三酯降低和HDL升高。假设经过检验。通过抑制游离脂肪酸反弹与前列腺素合成抑制剂。两项临床试验评估代谢综合征受试者，a)在静脉葡萄糖刺激期间，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品的离体分析。顾问是具有与主要目标相关的专业知识的成熟研究人员，并且在以强调所建议的那种转化医学而闻名的环境中具有成功指导的历史。该奖项将帮助候选人发展所需的技能和初步数据，以支持传统资助的申请，将有希望的发现转化为临床治疗环境。相关性（见说明）：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，甚至改善烟酸降低胆固醇。如果这是成功的，它可能会导致未来的策略，以改善烟酸治疗。（摘要结束）

项目成果

Niacin Alternatives for Dyslipidemia: Fool's Gold or Gold Mine? Part I: Alternative Niacin Regimens.

• DOI: 10.1007/s11883-016-0563-8
• 发表时间: 2016-02
• 期刊: Current atherosclerosis reports
• 影响因子: 5.8
• 作者: Dunbar RL;Goel H
• 通讯作者: Goel H

Could Exercise Metabolomics Pave the Way for Gymnomimetics?

• DOI: 10.1126/scitranslmed.3001188
• 发表时间: 2010-07-21
• 期刊: SCIENCE TRANSLATIONAL MEDICINE
• 影响因子: 17.1
• 作者: Burke, Megan F.;Dunbar, Richard L.;Rader, Daniel J.
• 通讯作者: Rader, Daniel J.