The Wake Forest Center for Botanical Lipids and Inflammatory Disease Prevention

维克森林植物脂质和炎症疾病预防中心

• 批准号: 8263134
• 负责人: FLOYD H CHILTON
• 金额: $ 146.99万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8263134
• 关键词: 11q12-q13; Acids; Address; Adult; Affect; African American; Alleles; American; Anthropology; Anti-Inflammatory Agents; Anti-inflammatory; Arachidonate 5-Lipoxygenase; Area; Asthma; Atherosclerosis; Back; Biochemical; Biodiversity; Biological; Biological Factors; Biological Markers; Biological Preservation; Biometry; Blood; Borago; Botanicals; Botany; Carbon; Cardiovascular Diseases; Caucasians; Caucasoid Race; Cell Differentiation process; Cells; Characteristics; Cholesterol; Chromosomes; Chromosomes, Human, Pair 11; Clinical Immunology; Clinical Research; Clinical Trials Design; Coenzyme A; Collaborations; Complement; Complementary and alternative medicine; Complex; Consultations; DNA; Data; Databases; Diabetes Mellitus; Dietary Fats; Disease; Distal; Doctor of Philosophy; Echium; Effectiveness; Eicosanoid Production; Eicosanoids; Ensure; Enzymes; Epidemiologist; Epoxy Compounds; Extrinsic asthma; Fatty Acid Desaturases; Fatty Acids; Fee-for-Service Plans; Flax; Frequencies; Funding; Gas Chromatography; Gene Cluster; Gene Expression; Gene Expression Regulation; Gene Family; Generations; Genes; Genetic; Genetic Polymorphism; Genetic Transcription; Genetic Variation; Genomics; Genotype; Goals; Grant; Health; Health Sciences; Human; Human Resources; Hypersensitivity; Immunity; Immunogenetics; Individual; Inflammation; Inflammation Mediators; Inflammatory; Inflammatory Response; Influentials; Institutes; Internal Medicine; International; Investigation; Island; Knockout Mice; Laboratories; Lead; Leadership; Leukocyte Trafficking; Leukocytes; Leukotriene C4; Leukotriene D4; Leukotriene E4; Leukotriene Production; Leukotrienes; Ligase; Link; Linseed Oil; Lipids; Low Density Lipoprotein Receptor; Maps; Mass Spectrum Analysis; Mediator of activation protein; Medicinal Plants; Medicine; Metabolic; Metabolic syndrome; Metabolism; Minor; Minority; Modality; Modeling; Molecular; Monitoring Clinical Trials; Mononuclear; Mus; Nonesterified Fatty Acids; Oils; Olive oil preparation; Olives - dietary; Pathway interactions; Patients; Phenotype; Phospholipase A2; Phospholipids; Physicians; Plant Oils; Plant Sources; Plants; Play; Population; Positioning Attribute; Prevention; Preventive; Principal Investigator; Process; Production; Prostaglandins; Public Health; Publishing; Race; Relative (related person); Research; Research Personnel; Research Project Grants; Resources; Role; Running; Sampling; Science; Screening procedure; Seeds; Serum; Signal Transduction; Site; Skiing; Source; Supplementation; TNFRSF5 gene; Techniques; Testing; Thromboxanes; Training; Transactivation; Transduction Gene; Triglycerides; United States National Institutes of Health; Universities; Unsaturated Fatty Acids; Variant; Work; arm; base; borage oil; cytokine; desaturase; design; dietary supplements; disorder prevention; epidemiology study; ethnic difference; experience; fatty acid metabolism; forest; genetic analysis; genetic epidemiology; granulocyte; in vivo; indexing; instrumentation; interest; lipid metabolism; liquid chromatography mass spectrometry; macrophage; mast cell; medical schools; member; monocyte; novel; peripheral blood; prevent; professor; programs; public health relevance; quality assurance; research study; response; trafficking; transcription factor

DESCRIPTION (provided by applicant): The Center for Botanical Lipids and Inflammatory Disease Prevention is a new version of a P50 at Wake Forest University Health Sciences that has been continuously funded since 2005. Research over the past 50 years has shown that both systemic and localized inflammation play an important role in the onset and progression of destructive diseases such as cardiovascular disease, metabolic syndrome/diabetes and allergic asthma. The overall goal of this Center is to delineate the molecular mechanisms by which botanical oils prevent or impact these diseases with a particular focus on immunity and inflammation. The central hypothesis of the Center is that medium chain poly-unsaturated fatty acids (PUFAs) in botanical oils and their metabolites impact several key mechanisms (including altering pro-and anti-inflammatory mediator production and blocking inflammatory gene expression) that inhibit inflammatory processes. A secondary hypothesis is that that the metabolism and effectiveness of PUFA-based botanical dietary supplements is strongly associated with genetic polymorphisms in the fatty acid desaturase (FADS 1-3) cluster on chromosome 11 in a region known as 11q12-q13. This chromosomal region has repeatedly been linked to pro-inflammatory conditions. This Center brings together investigators from five internationally-recognized lipid groups and a world-renowned human genomics center to examine cellular and molecular mechanisms by which PUFAs within botanical oils impact human health. Selected botanical oils and combinations (including olive, flax seed, borage seed and echium seed oils) found in supplements are used to test key hypotheses. Projects 1 and 2 examine the mechanisms leading to the pleiotropic effects of botanical PUFAs on macrophage/ monocyte activation, inflammatory states and eicosanoid generation related to atherosclerosis and asthmatic inflammation, respectively. Project 3 examines the critical role genetic variations in the FADS cluster plays in determining PUFA levels and investigates how specific variations in that cluster are associated with the effectiveness of PUFA-based botanicals supplements in metabolic syndrome/diabetes. The interactive and synergistic Projects and Cores have a strong, contemporary and translational scientific basis and should allow this scientific team to identify additional mechanisms and identify human individuals and populations that are most likely to be affected by PUFA- based botanical supplements. PUBLIC HEALTH RELEVANCE: Thirty-eight percent of adult Americans are using complementary and alternative medicine modalities. The most commonly used modalities are natural products enriched with PUFAs (37 % of natural products). The key purpose of this Center is determine the molecular mechanisms by which medium chain PUFAs in botanical oils prevent of complex diseases such as CVD, asthma or metabolic syndrome and to determine the populations where they are most likely to be effective.

描述（由申请人提供）：植物脂质和炎症疾病预防中心是维克森林大学健康科学中心 P50 的新版本，自 2005 年以来一直得到持续资助。过去 50 年的研究表明，全身和局部炎症在心血管疾病、代谢综合征/糖尿病和过敏等破坏性疾病的发生和进展中发挥着重要作用。 哮喘。该中心的总体目标是描绘植物油预防或影响这些疾病的分子机制，特别关注免疫和炎症。该中心的核心假设是植物油中的中链多不饱和脂肪酸（PUFA）及其代谢物影响抑制炎症过程的几个关键机制（包括改变促炎和抗炎介质的产生以及阻断炎症基因表达）。第二个假设是，基于 PUFA 的植物膳食补充剂的代谢和有效性与 11 号染色体 11q12-q13 区域的脂肪酸去饱和酶 (FADS 1-3) 簇的遗传多态性密切相关。该染色体区域已多次与促炎性疾病相关。 该中心汇集了来自五个国际公认的脂质组和一个世界著名的人类基因组中心的研究人员，研究植物油中的多不饱和脂肪酸影响人类健康的细胞和分子机制。补充剂中的精选植物油和组合（包括橄榄油、亚麻籽油、琉璃苣籽油和蓝蓟籽油）用于测试关键假设。项目 1 和 2 研究了植物性 PUFA 分别对与动脉粥样硬化和哮喘炎症相关的巨噬细胞/单核细胞活化、炎症状态和类二十烷酸生成产生多效作用的机制。项目 3 检查 FADS 簇中的遗传变异在确定 PUFA 水平方面所起的关键作用，并研究该簇中的特定变异如何与基于 PUFA 的植物补充剂在代谢综合征/糖尿病中的有效性相关。互动和协同的项目和核心具有强大的、当代的和转化性的科学基础，应该使这个科学团队能够确定额外的机制，并确定最有可能受到基于多不饱和脂肪酸的植物补充剂影响的人类个体和人群。 公共卫生相关性：38% 的美国成年人正在使用补充和替代医学方式。最常用的方式是富含 PUFA 的天然产品（占天然产品的 37%）。该中心的主要目的是确定植物油中的中链多不饱和脂肪酸预防心血管疾病、哮喘或代谢综合征等复杂疾病的分子机制，并确定它们最有可能有效的人群。