Ph.D., Pharmacology and Toxicology - UC Davis USDA, ARS, Western Human Nutrition Research Center Office: 430 West Health Phone: (530) 752-1009 Fax: (530) 752-5271
Ph.D., Pharmacology and Toxicology - UC Davis
USDA, ARS, Western Human Nutrition Research Center
Office: 430 West Health
Phone: (530) 752-1009
Fax: (530) 752-5271
Dr. John Newman is an avid collaborator with researchers in the WHNRC, the
Dr. Newman is a
Investigations surrounding the endogenous role of the soluble epoxide hydrolase were at the root of these investigations. They have since expanded to encompass products of the major lipid oxygenases including prostanoids and various eicosanoids as well as analogous materials generated for eighteen and twenty-two carbon lipids. These analytical profiling efforts have more recently broadened to investigate other bioactive lipid mediators involved in the regulation of energy balance and body mass, including a suite of endocannabinoids. The role of these regulatory pathways have been explored in inflammation, renal function, vascular regulation and disease, blood pressure regulation and both male and female reproductive physiology. More recently, these tools have been turned on the lipoprotein particle, and subtle structural changes in these particles are beginning to be observed.
During his research career, Dr. Newman has written or supported more than 60 articles in peer-reviewed journals. He has served as a peer reviewer for an array of journals including the American Journal of Clinical Nutrition, the British Journal of Nutrition, the Journal of Chromatography, Archives in Biochemistry and Biophysics, Chemosphere, Proteomics, and Metabolomics. In addition, Dr. Newman is a member in good standing in the Metabolomics Society and the American Chemical Society.
The Newman laboratory research program is investigating the impact of dietary lipids on process associated with obesity and inflammation, how these effects alter the structure and function of lipoprotein particles, and how these cumulative changes produce coordinated changes in tissue lipid metabolism and signaling. At the heart of this research is an effort to understand whether fine-tuning an individual’s dietary lipid intake can improve body weight and health beyond those recommended to the general population by the U.S. Dietary Guidelines. To achieve these goals, the group combines high information content analytical chemistry with biochemistry, human interventions, as well as cell and molecular biology to investigate the impact of dietary lipid content and composition on PPAR-dependent signaling, inflammatory status, adipocyte growth and differentiation, and changes in systemic eicosanoid and endocannabinoid system tones. These research goals promise to extend and complement the WHNRC’s impact in the area of dietary fats on health outcomes accomplished by previous ARS scientists Drs. Iacono, Nelson, Kelly and Hwang over the past 40 years.
Specific Research Areas
Do lipoprotein particles deliver bioactive lipids to peripheral tissues? A central hypothesis being tested in the laboratory is that lipoprotein particles transport bioactive signaling lipids to peripheral tissues, influencing homeostatic set points, and that this process is influenced by dietary lipid compositions. With the exception of small free fatty acid and lyso-phosphotide pools associated with albumin, plasma lipids are esterified within lipoproteins, where apolipoproteins facilitate systemic lipid trafficking. Moreover, the dietary saturated/monounsaturated/polyunsaturated fatty acid balance has significant impacts on the structure and function of lipoprotein particles and lipid trafficking, with consequences on vascular health. For instance, high omega-3 fatty acid consumption can have both anti-inflammatory and anti-hypertriglyceridemic cardioprotective effects. In obese animals, high n3 LC-PUFA diets can also reduce weight and hypothalamic drivers of hunger, while increasing anorexigenic adipokine production, and improve central sensitivity to these adipokines. While LpL-mediated lipolysis dominates VLDL clearance, whole particle uptake of VLDL1 accounts for 20-30% of clearance in normolipidemic humans, and dominates LDL and HDL clearance. Moreover, fish oil feeding increases adipose expression of the oxo-LDL receptor CD36 through the PPAR-γ dependent mechanisms. Since cell growth and differentiation is influenced by PUFA metabolites, including eicosanoids and endocannabinoids produced within cells, delivery of these agents preformed to cells could have profound effects on cellular homeostasis. Our earlier studies have shown that obesity increases concentrations of oxygenated lipids esterified into lipoprotein particles, that these lipids are released by lipoprotein lipase, and their release is associated with a postprandial inflammatory response in the vascular endothelium. In addition, we have seen that n3 LC-PUFA supplementation significantly alters the profiles of circulating oxygenated PUFAs. Current efforts in the laboratory are designed to evaluate the ramifications of these altered lipoprotein structures on the function of exposed cellular systems including vascular and adipose cell types.
Does variance in LC-PUFA biosynthesis influence the efficacy of dietary fish oil? Dietary PUFAs in the
Selected Publications & Patent Applications
Pedersen, T.L., W.R. Keyes, S. Shahab-Ferdows, L.H. Allen, J.W. Newman. 2011. Methylmalonic Acid Quantification in Low Serum Volumes Using UPLC-MS/MS. J. Chromatogr. B. 879, 1502-6. doi: 10.1016/j.jchromb.2011.03.039.
Bendsen, N.T., S. Stender, P.B. Szecsi, S.B. Pedersen, S. Basu, L.I. Hellgren, J.W. Newman, T.M. Larsen, S.B. Haugaard, A. Astrup. 2011. Effect of industrially produced trans fat on markers of systemic inflammation: evidence from a randomized trial in women. J. Lipid Res. 52: 1821-1828. PMID: 21795740.
Armstrong, P., D.S. Kelley, J.W. Newman, F. Staggers Sr., J. Hartiala, H. Allayee, C.B. Stephensen. 2012. Arachidonate 5-Lipoxygenase Gene Variants Affect Response to Fish Oil Supplementation by Healthy African Americans. J. Nutr. 142(8):1417-28. Epub 2012 Jun 27. PMID: 22739369.
Keenan, A.H., T.L. Pedersen, K. Fillaus, G.C. Shearer, J.W. Newman. 2012. Basal omega-3 fatty acid status affects fatty acid and oxylipin responses to high-dose n3-HUFA in healthy volunteers. J. Lipid Res. 53:1662-1669. PMID: 22628615. doi: 10.1194/jlr.P025577.
Strassburg, K., A.M.L. Huijbrechts, K. Kortekaas, J. Lindeman, T.L. Pedersen, A. Dane, R. Berger, A. Brenkman, T. Hankemeier, J. van Duynhoven, E. Kalkhoven, J.W. Newman, R. Vreeken. 2012. Quantitative Profiling of Oxylipins through Comprehensive LC-MS/MS Analysis: Application in cardiac surgery. Anal. Bianal. Chem. 404(5):1413-26 [Epub: Jul 20, 2012]. PMID: 22814969.
Grapov, D., J.W. Newman. 2012. imDEV: a Graphical User Interface to R Multivariate Analysis Tools in Microsoft Excel. Bioinformatics. 28(17):2288-90. [Epub: Jul 19, 2012]. doi: 10.1093/bioinformatics/bts439. PMID: 22815358.
Sun C., K. Alkhoury, Y.I. Wang, G.A. Foster, C.E. Radecke, K. Tam, C.M. Edwards, M.T. Facciotti, E.J. Armstrong, A.A. Knowlton, J.W. Newman, A.G. Passerini, S.I. Simon. 2012. IRF-1 and miRNA126 modulate inflammatory VCAM-1 expression in response to a high fat meal. Circ. Res. 111(8):1054-64. [Epub: Aug 8, 2012]. PMID: 22874466.
Grapov D., S.H. Adams, T.L. Pedersen, W.T. Garvey, J.W. Newman. 2012. Type 2 diabetes associated changes in circulating non-esterified fatty acids, oxylipins, and endocannabinoids. PLoS ONE. 7(11): e48852. doi:10.1371/journal.pone.0048852.
Bruins, M.J., A.D. Dane, K. Strassburg, R.J. Vreeken, J.W. Newman, N. Salem Jr., C. Tyburczy, J.T. Brenna. Plasma Oxylipin Profiling Identifies Polyunsaturated Vicinal Diols as Responsive to Arachidonic Acid and Docosahexaenoic Acid Intake in Growing Piglets. J Lipid Res. 2013 Mar 29. [Epub] PMID: 23543770.