The Wake Forest Center for Botanical Lipids and Inflammatory Disease Prevention

描述（由申请人提供）：植物性脂质和炎症性疾病预防中心是维克森林大学健康科学P50的新版本，自2005年以来一直得到资助。过去50年的研究表明，全身性和局部炎症在破坏性疾病（如心血管疾病、代谢综合征/糖尿病和过敏性哮喘）的发病和进展中起重要作用。该中心的总体目标是描述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。该中心的中心假设是，植物油中的中链多不饱和脂肪酸（PUFA）及其代谢产物影响抑制炎症过程的几种关键机制（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号染色体上称为11 q12-q1 - 3区域的脂肪酸去饱和酶（FADS 1-3）簇的遗传多态性密切相关。该染色体区域多次与促炎性疾病有关。 该中心汇集了来自五个国际公认的脂质组和世界知名的人类基因组学中心的研究人员，以研究植物油中PUFA影响人类健康的细胞和分子机制。在补充剂中发现的选定的植物油和组合（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分别研究了植物PUFA对巨噬细胞/单核细胞活化、炎症状态和与动脉粥样硬化和哮喘炎症相关的类花生酸生成的多效性作用的机制。项目3研究了FADS簇中的遗传变异在确定PUFA水平方面的关键作用，并研究了该簇中的特定变异如何与基于PUFA的植物性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，当代的和转化的科学基础，并应允许该科学团队确定其他机制，并确定最有可能受到基于PUFA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模式。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PUFA预防复杂疾病（如CVD，哮喘或代谢综合征）的分子机制，并确定它们最有可能有效的人群。

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.