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.

Agency
National Institute of Health (NIH)
Type
Specialized Center (P50)
Project #
5P50AT002782-10
Application #
8727444
Study Section
Special Emphasis Panel (ZAT1)
Program Officer
Hopp, Craig
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Physiology
Type
Schools of Medicine
DUNS #
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157
Chung, Soonkyu; Cuffe, Helen; Marshall, Stephanie M et al. (2014) Dietary cholesterol promotes adipocyte hypertrophy and adipose tissue inflammation in visceral, but not in subcutaneous, fat in monkeys. Arterioscler Thromb Vasc Biol 34:1880-7
Zemski Berry, Karin A; Gordon, William C; Murphy, Robert C et al. (2014) Spatial organization of lipids in the human retina and optic nerve by MALDI imaging mass spectrometry. J Lipid Res 55:504-15
Mathias, Rasika A; Pani, Vrindarani; Chilton, Floyd H (2014) Genetic Variants in the FADS Gene: Implications for Dietary Recommendations for Fatty Acid Intake. Curr Nutr Rep 3:139-148
Howard, Timothy D; Mathias, Rasika A; Seeds, Michael C et al. (2014) DNA methylation in an enhancer region of the FADS cluster is associated with FADS activity in human liver. PLoS One 9:e97510
Bi, Xin; Zhu, Xuewei; Gao, Chuan et al. (2014) Myeloid cell-specific ATP-binding cassette transporter A1 deletion has minimal impact on atherogenesis in atherogenic diet-fed low-density lipoprotein receptor knockout mice. Arterioscler Thromb Vasc Biol 34:1888-99
Jiang, Yan; Djuric, Zora; Sen, Ananda et al. (2014) Biomarkers for personalizing omega-3 fatty acid dosing. Cancer Prev Res (Phila) 7:1011-22
Laidlaw, Tanya M; Cutler, Anya J; Kidder, Molly S et al. (2014) Prostaglandin E2 resistance in granulocytes from patients with aspirin-exacerbated respiratory disease. J Allergy Clin Immunol 133:1692-701.e3
Klomsiri, Chananat; Rogers, LeAnn C; Soito, Laura et al. (2014) Endosomal H2O2 production leads to localized cysteine sulfenic acid formation on proteins during lysophosphatidic acid-mediated cell signaling. Free Radic Biol Med 71:49-60
Chilton, Floyd H; Murphy, Robert C; Wilson, Bryan A et al. (2014) Diet-gene interactions and PUFA metabolism: a potential contributor to health disparities and human diseases. Nutrients 6:1993-2022
Liu, Tao; Laidlaw, Tanya M; Katz, Howard R et al. (2013) Prostaglandin E2 deficiency causes a phenotype of aspirin sensitivity that depends on platelets and cysteinyl leukotrienes. Proc Natl Acad Sci U S A 110:16987-92

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