Genomes and Genes
The Wake Forest Center for Botanical Lipids and Inflammatory Disease Prevention
Principal Investigator: Floyd H Chilton
Abstract: 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.
Funding Period: 2005-04-01 - 2015-08-31
more information: NIH RePORT
- Dietary fat-induced alterations in atherosclerosis are abolished by ACAT2-deficiency in ApoB100 only, LDLr-/- miceThomas A Bell
Wake Forest University School of Medicine, Department of Pathology Lipid Sciences, Medical Center Blvd, Winston Salem, NC 27157, USA
Arterioscler Thromb Vasc Biol 27:1396-402. 2007..We hypothesized that when ACAT2 activity is removed by gene deletion, hepatic CE synthesis and secretion would be minimal and, as a result, dietary fat-related differences in atherosclerosis would be eliminated...
- Adaptive evolution of the FADS gene cluster within AfricaRasika A Mathias
Division of General Internal Medicine, Department of Medicine, The Johns Hopkins University, Baltimore, Maryland, United States of America
PLoS ONE 7:e44926. 2012....
- Major urinary metabolites of 6-keto-prostaglandin F2α in miceDmitry V Kuklev
Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109, USA
J Lipid Res 54:1906-14. 2013..The 6-keto-PGF derivatives are not formed by free radical mechanisms that generate isoprostanes, and thus, these metabolites provide an unbiased marker for utilization of EPA by cyclooxygenases...
- Stearidonic and γ-linolenic acids in echium oil improves glucose disposal in insulin resistant monkeysK Kavanagh
Wake Forest School of Medicine, Department of Pathology, Winston Salem, NC 27127, USA
Prostaglandins Leukot Essent Fatty Acids 89:39-45. 2013..Glucose disposal was improved after EO consumption. These data suggest that PUFAs in EO supplementation have the capacity to alter circulating, RBC and muscle LC-PUFA levels and improve glucose tolerance in insulin-resistant monkeys...
- Echium oil reduces plasma triglycerides by increasing intravascular lipolysis in apoB100-only low density lipoprotein (LDL) receptor knockout miceLolita M Forrest
Department of Pathology Section on Lipid Sciences, Wake Forest School of Medicine, Winston Salem, NC 27157, USA
Nutrients 5:2629-45. 2013..Finally, EO may substitute for FO to reduce plasma TG concentrations, but not hepatic steatosis in this mouse model. ..
- Prostaglandin E2 deficiency causes a phenotype of aspirin sensitivity that depends on platelets and cysteinyl leukotrienesTao Liu
Departments of Medicine and Pediatrics, Harvard Medical School, Boston, MA 02115
Proc Natl Acad Sci U S A 110:16987-92. 2013..The findings suggest applications of antiplatelet drugs or TP receptor antagonists for the treatment of AERD. ..
- Impact of botanical oils on polyunsaturated fatty acid metabolism and leukotriene generation in mild asthmaticsJonathan P Arm
Department of Physiology Pharmacology, Wake Forest School of Medicine, Medical Center Blvd, 27157, Winston Salem, NC, USA
Lipids Health Dis 12:141. 2013....
- The serine hydrolase ABHD6 Is a critical regulator of the metabolic syndromeGwynneth Thomas
Department of Pathology, Section on Lipid Sciences, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA
Cell Rep 5:508-20. 2013..Collectively, these data suggest that ABHD6 inhibitors may serve as therapeutics for obesity, nonalcoholic fatty liver disease, and type II diabetes. ..
- Cutting edge: Leukotriene C4 activates mouse platelets in plasma exclusively through the type 2 cysteinyl leukotriene receptorHannah E Cummings
Jeff and Penny Vinik Center for Allergic Disease Research, Boston, MA 02115
J Immunol 191:5807-10. 2013..Nascent LTC4 may activate platelets at a synapse with granulocytes before it is converted to LTD4, promoting mediator generation and the formation of leukocyte-platelet complexes that facilitate inflammation. ..
- Spatial organization of lipids in the human retina and optic nerve by MALDI imaging mass spectrometryKarin A Zemski Berry
Department of Pharmacology, University of Colorado Denver, Aurora, CO 80045 and
J Lipid Res 55:504-15. 2014....
- Endosomal H2O2 production leads to localized cysteine sulfenic acid formation on proteins during lysophosphatidic acid-mediated cell signalingChananat Klomsiri
Department of Biochemistry, Wake Forest School of Medicine, Winston Salem, NC 27157, USA Electronic address
Free Radic Biol Med 71:49-60. 2014..DCP-Rho1 may be a particularly useful protein oxidation imaging agent enabling spatial resolution due to the transient nature of the sulfenic acid intermediate it detects. ..
- Myeloid cell-specific ATP-binding cassette transporter A1 deletion has minimal impact on atherogenesis in atherogenic diet-fed low-density lipoprotein receptor knockout miceXin Bi
From the Department of Pathology Section on Lipid Sciences X B, X Z, C G, S S, Q C, M L, E B, A K G, M D W, A L B, J S P and Department of Biochemistry, Wake Forest School of Medicine, Winston Salem, NC J S P
Arterioscler Thromb Vasc Biol 34:1888-99. 2014..Myeloid-specific ATP-binding cassette transporter A1 knockout mice in the low-density lipoprotein (LDL) receptor knockout C57BL/6 background were developed to address this question...
- DNA methylation in an enhancer region of the FADS cluster is associated with FADS activity in human liverTimothy D Howard
Center for Genomics and Personalized Medicine Research, Center for Public Health Genomics, Wake Forest School of Medicine, Winston Salem, North Carolina, United States of America
PLoS ONE 9:e97510. 2014..In support of this hypothesis, methylation levels of the most significant probe were strongly associated with FADS1 and, to a lesser degree, FADS2 activities...
- Omega-3 fatty acids ameliorate atherosclerosis by favorably altering monocyte subsets and limiting monocyte recruitment to aortic lesionsAmanda L Brown
Department of Pathology, Section on Lipid Sciences, Wake Forest School of Medicine, Medical Center Blvd, Winston Salem, NC 27157 1040, USA
Arterioscler Thromb Vasc Biol 32:2122-30. 2012..Fish oil, containing omega-3 fatty acids, attenuates atherosclerosis. We hypothesized that omega-3 fatty acid-enriched oils are atheroprotective through alteration of monocyte subsets and their trafficking into atherosclerotic lesions...
- Prostaglandin E2 deficiency uncovers a dominant role for thromboxane A2 in house dust mite-induced allergic pulmonary inflammationTao Liu
Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 109:12692-7. 2012..Thus, PGE(2) controls the strength of TP receptor signaling as a major bronchoprotective mechanism, carrying implications for the pathobiology and therapy of asthma...
- Echium oil reduces plasma lipids and hepatic lipogenic gene expression in apoB100-only LDL receptor knockout micePing Zhang
Section on Lipid Sciences, Department of Pathology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA
J Nutr Biochem 19:655-63. 2008..In conclusion, EO may provide a botanical alternative to FO for reduction of plasma TG concentrations...
- LDL cholesteryl oleate as a predictor for atherosclerosis: evidence from human and animal studies on dietary fatChiara Degirolamo
Department of Pathology, Section on Lipid Sciences, Wake Forest University School of Medicine, Winston Salem NC 27157, USA
J Lipid Res 50:S434-9. 2009..Polyunsaturated fat appears to provide atheroprotection, at least in part, because it limits the accumulation of cholesteryl oleate in favor of cholesteryl linoleate in plasma lipoproteins...
- Toll-like receptor signaling links dietary fatty acids to the metabolic syndromeMichael B Fessler
Department of Pathology, Section on Lipid Sciences, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157 1040, USA
Curr Opin Lipidol 20:379-85. 2009..Here we examine emerging molecular evidence that SFAs directly engage pathways of innate immunity, thereby promoting inflammatory aspects of the metabolic syndrome...
- Stearoyl-coenzyme A desaturase 1 inhibition and the metabolic syndrome: considerations for future drug discoveryJ Mark Brown
Department of Pathology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157 1040, USA
Curr Opin Lipidol 21:192-7. 2010..However, recent studies warn of potentially harmful consequences of SCD1 inhibition. The purpose of this review is to discuss recent insights into the potential for SCD1 inhibitors as viable metabolic syndrome therapeutics...
- Effect of a multifaceted, church-based wellness program on metabolic syndrome in 41 overweight or obese congregantsPriscilla Ivester
Center for Botanical Lipids, 391 Technology Way, Winston Salem, NC 27101, USA
Prev Chronic Dis 7:A81. 2010..Our objective was to determine the effect of a short-term, multifaceted wellness program carried out in a church setting on weight, metabolic syndrome, and self-reported wellness...
- Depression and altered serum lipids in cynomolgus monkeys consuming a Western dietFloyd H Chilton
Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston Salem, NC 27157, USA
Physiol Behav 104:222-7. 2011....
- Dietary fish oil modestly attenuates the effect of age on diastolic function but has no effect on memory or brain inflammation in aged ratsSusan Sergeant
Department of Biochemistry, Wake Forest University School of Medicine, Winston Salem, NC 27157 1009, USA
J Gerontol A Biol Sci Med Sci 66:521-33. 2011..These data raise the possibility that FO supplementation for purposes of cardiac and brain protection may need to occur earlier in the life span...
- The impact of FADS genetic variants on ω6 polyunsaturated fatty acid metabolism in African AmericansRasika A Mathias
Division of General Internal Medicine, Department of Medicine, The GeneSTAR Research Program, The Johns Hopkins University, Baltimore, MD 21224, USA
BMC Genet 12:50. 2011....
- Differences in arachidonic acid levels and fatty acid desaturase (FADS) gene variants in African Americans and European Americans with diabetes or the metabolic syndromeSusan Sergeant
The Center for Botanical Lipids and Inflammatory Disease Prevention, Wake Forest School of Medicine, Winston Salem, NC 27157, USA
Br J Nutr 107:547-55. 2012..These differences may provide a genetic mechanism contributing to health disparities between populations of African and European descent...
- Adipose tissue ATP binding cassette transporter A1 contributes to high-density lipoprotein biogenesis in vivoSoonkyu Chung
Department of Pathology Section on Lipid Sciences, Wake Forest School of Medicine, Winston Salem, NC, USA
Circulation 124:1663-72. 2011..However, the extent to which AT ABCA1 expression contributes to HDL biogenesis in vivo is unknown...
- Echium oil reduces atherosclerosis in apoB100-only LDLrKO miceLolita M Forrest
Department of Pathology Section on Lipid Sciences, Wake Forest School of Medicine, Winston Salem, NC 27157, United States
Atherosclerosis 220:118-21. 2012..Echium oil contains stearidonic acid (SDA; 18:4, n-3), which is metabolized to EPA in humans and mice, resulting in decreased plasma triglycerides...
- Cysteinyl leukotriene overproduction in aspirin-exacerbated respiratory disease is driven by platelet-adherent leukocytesTanya M Laidlaw
Department of Medicine, Harvard Medical School, Boston, MA, USA
Blood 119:3790-8. 2012....
- Diet-gene interactions and PUFA metabolism: a potential contributor to health disparities and human diseasesFloyd H Chilton
The Center for Botanical Lipids and Inflammatory Disease Prevention, Wake Forest School of Medicine, Winston Salem, NC 27157, USA
Nutrients 6:1993-2022. 2014....
- Inflammatory responses of vascular cellsPaul L Fox; Fiscal Year: 2013..abstract_text> ..
- The Center for Native and Pacific Health Disparities ResearchMARJORIE K LEIMOMI MALA MAU; Fiscal Year: 2013..5) To prepare and empower our diverse Native and Pacific People communities to take ownership of their own health and wellness. ..
- Hopkins Center for Health Disparities SolutionsTHOMAS ALEXIS LAVEIST; Fiscal Year: 2013..abstract_text> ..
- EARLY EVENTS IN ALZHEIMER PATHOGENESISSUE TILTON GRIFFIN; Fiscal Year: 2013..The synergy between our aims, approaches, and measures will enable us to meet our goal of defining early cellular interactions toward development of rational interventions in AD. ..
- Molecular and Cellular Basis for Digestive DiseasesRichard M Peek; Fiscal Year: 2013..The Administrative Core also contains Biostatistics and Enrichment Programs and oversees the financial management and operation of the VDDRC. ..
- Semi-volatile PCBs: Sources, Exposures, ToxicitiesLarry W Robertson; Fiscal Year: 2013..These data and dietary studies in the last Aim will provide a scientific basis for risk assessment and advice for stakeholders with the ultimate goal to protect highly-exposed individuals and populations. ..
- PAHs: New Technologies and Emerging Health RisksDavid E Williams; Fiscal Year: 2013..Accomplishing these goals will provide significant scientific advancement and improve the quality of life for impacted communities. ..
- Basic and Clinical Studies of Cystic FibrosisRaymond A Frizzell; Fiscal Year: 2013..The Core Center will operate a Pilot and Feasibility Program to bring new investigators into CF research. This Center emphasizes the translation of basic knowledge into applied therapeutics. ..