NIH CARBON Program:
Botanical Lipids and Inflammatory Disease Prevention: 2005-2015

Results in NIHReporter

2005 – 2010

Center for Botanical Lipids

Director: Floyd H. Chilton, Ph.D.
Institutions: Wake Forest University, Winston-Salem, NC; Brigham and Women's Hospital, Boston, MA

All projects in the center focused on specific fatty acids derived from a single biochemical pathway involving the elongation and desaturation of n-3 and n-6 fatty acids. Center scientists examined biological mechanisms and clinical applications of botanical sources of polyunsaturated fatty acids which may have benefit in the prevention and treatment of anti-inflammatory diseases such as atherosclerosis and asthma. Research projects included: Mechanisms of Atherosclerosis Prevention by Flaxseed Oil;  Echium Oil Triglyceride Metabolism and Atherosclerosis; Mechanism of Leukotriene Inhibition by Botanical Oils; and Treatment of Bronchial Asthma with Borage Seed Oil. 

Highlighted Publications

Chilton FH, Rudel LL, Parks JS, Arm JP, Seeds MC. Mechanisms by which botanical lipids affect inflammatory disorders. Am J Clin Nutr. 2008;87(2):498S-503S. doi:10.1093/ajcn/87.2.498Sexternal link disclaimer
This manuscript focused on the key molecular and genetic mechanisms by which botanical lipids in dietary supplements regulate the production of lipid mediators involved in inflammatory and hyperlipidemic diseases. 

Mathias RA, Vergara C, Gao L, et al. FADS genetic variants and omega-6 polyunsaturated fatty acid metabolism in a homogeneous island population. J Lipid Res. 2010;51(9):2766-2774. doi:10.1194/jlr.M008359external link disclaimer
This was one of the original papers which demonstrated that genetic variants in the Delta-5 desaturase (FADS1) enzymatic step regulate the efficiency of conversion of botanical polyunsaturated fatty acids to biologically-active long chain polyunsaturated fatty acids.

Weaver KL, Ivester P, Chilton JA, Wilson MD, Pandey P, Chilton FH. The content of favorable and unfavorable polyunsaturated fatty acids found in commonly eaten fish [published correction appears in J Am Diet Assoc. 2008 Oct;108(10):1785]. J Am Diet Assoc. 2008;108(7):1178-1185. doi:10.1016/j.jada.2008.04.023external link disclaimer
This highly cited manuscript characterized the fatty acid chemistry of commonly consumed fish, with a particular focus on the four most commonly consumed farmed fish.

Weaver KL, Ivester P, Seeds M, Case LD, Arm JP, Chilton FH. Effect of dietary fatty acids on inflammatory gene expression in healthy humans. J Biol Chem. 2009;284(23):15400-15407. doi:10.1074/jbc.M109.004861external link disclaimer  PMCID: PMC2708836
This highly cited paper demonstrated how botanical and marine polyunsaturated fatty acids may exert their clinical effects via their capacity to regulate the expression of signal transduction genes and genes for pro-inflammatory cytokines.
 

2010 – 2015

Botanical Lipids and Inflammatory Disease Prevention

Director: Floyd H. Chilton, Ph.D.
Institution: Wake Forest University, Winston-Salem, NC
Partners: University of Colorado Health Sciences, Aurora, CO; Brigham and Women's Hospital, Boston, MA; Bent Creek Institute, Asheville, NC; Johns Hopkins University, Baltimore, MD

The goal of this Center in its second 5-year cycle was to delineate the molecular mechanisms by which botanical oils prevent or affect disease (cardiovascular disease, asthma and metabolic syndrome) with a particular focus on immunity and inflammation. The center studied different populations to determine whether botanical lipids are more likely to be effective in particular subpopulations. Research projects included: Atheroprotective Mechanisms of Borage and Echium Oils; Mechanisms of Actions of Botanical Lipids on Effector Cells of Asthma; and Role of Fatty Acid Desaturase Polymorphisms in Determining the Effectiveness of PUFA-based Botanical Supplements in Humans. 

Highlighted Publications

Hester AG, Murphy RC, Uhlson CJ, et al. Relationship between a common variant in the fatty acid desaturase (FADS) cluster and eicosanoid generation in humans. J Biol Chem. 2014;289(32):22482-22489. doi:10.1074/jbc.M114.579557external link disclaimer PMCID: PMC4139254
While previous studies had demonstrated that FADS cluster variation impacted levels of long chain polyunsaturated fatty acids, this study demonstrated that these changes were also observed with concentrations of biologically-active eicosanoids that impact human diseases.

Lee TC, Ivester P, Hester AG, et al. The impact of polyunsaturated fatty acid-based dietary supplements on disease biomarkers in a metabolic syndrome/diabetes population. Lipids Health Dis. 2014;13:196. Published 2014 Dec 16. doi:10.1186/1476-511X-13-196external link disclaimer PMCID: PMC4290816
This short-term clinical trial demonstrated that a botanical oil combination or fish oil improves clinical biomarkers associated with type 2 diabetes or metabolic syndrome.

Mathias RA, Fu W, Akey JM, et al. Adaptive evolution of the FADS gene cluster within Africa. PLoS One. 2012;7(9):e44926. doi:10.1371/journal.pone.0044926external link disclaimer  PMCID: PMC3446990
This paper provided evolutionary evidence that high efficiency converter alleles in the FADS gene cluster (that convert botanical polyunsaturated fatty acids to biologically-active long chain polyunsaturated fatty acids) were driven to near fixation in African populations by positive selection ∼85 kya.

Sergeant S, Hugenschmidt CE, Rudock ME, et al. Differences in arachidonic acid levels and fatty acid desaturase (FADS) gene variants in African Americans and European Americans with diabetes or the metabolic syndrome. Br J Nutr. 2012;107(4):547-555. doi:10.1017/S0007114511003230external link disclaimer PMCID: PMC3494092
This highly cited paper was one of two from the Wake Forest Botanical Center which first demonstrated that African ancestry populations have dramatically different frequencies of FADS variants that modulate the conversion of botanical polyunsaturated fatty acids to biologically-active long chain polyunsaturated fatty acids.

 

 Prior CARBON Awards | NIH CARBON Program