Laura den Hartigh, PhD
Research Assistant Professor, Department of Medicine, Division of Metabolism, Endocrinology and Nutrition
Email Address: email@example.com
Division of Metabolism, Endocrinology and Nutrition Website: http://depts.washington.edu/metab/
Dr. den Hartigh received her Ph.D. in Molecular, Cellular, and Integrated Physiology from the University of California, Davis in 2008, with a Designated Emphasis in Biotechnology. She began her postdoctoral training in the laboratory of Dr. Dennis Wilson, D.V.M, Ph.D. at the University of California, Davis, and completed her training in the laboratory of Dr. Alan Chait, M.D. at the University of Washington. She is currently a Research Assistant Professor of Medicine in the Diabetes and Obesity Center of Excellence at the University of Washington.
The prevalence of obesity and associated diseases is rapidly reaching epidemic proportions. Representing the major cellular constituent of adipose tissue, adipocytes are now regarded as prominent players in the metabolic as well as hormonal regulation of adiposity. Despite the fundamental role adipose tissue plays in whole body metabolism, nutritive mechanisms that contribute to its maintenance in the context of obesity remain poorly understood. Dr. den Hartigh’s research focuses on the effects of nutrient excess on cellular metabolism, with particular attention given to the effects of fatty acids on cell types associated with the development of obesity such as adipocytes and monocytes/macrophages.
Inflammation of visceral adipose tissue is thought to be associated with insulin resistance, systemic inflammation and atherosclerosis. Furthermore, adipose tissue inflammation is characterized by immune cell accumulation, with macrophages as the predominant infiltrating cell type. We are particularly interested in the role of excess nutrients derived from glucose or various fatty acids on adipose tissue inflammation. We use mouse models to study how obesity derived by nutrient excess leads to adipose tissue and systemic inflammation. A particular nutrient of interest is 10,12 CLA, which has been shown to reduce triglyceride storage and increase energy expenditure by adipocytes and has therefore been marketed as a weight loss supplement. However, in addition to the beneficial effects of reduced adiposity, 10,12 CLA induces detrimental effects such as inflammation, insulin resistance and oxidative stress. We utilize in vitro and murine models to examine the complex effects of 10,12 CLA supplementation on adipocyte biology.
den Hartigh LJ, Wang S, Goodspeed L, Ding Y, Averill M, Subramanian S, Wietecha T, O’Brien KD, Chait A (2014). Deletion of Serum Amyloid A3 Improves High Fat High Sucrose Diet-Induced Adipose Tissue Inflammation and Hyperlipidemia in Female Mice. PLoS One. 2014 Sep 24;9(9):e108564.
den Hartigh LJ, Han CY, Wang S, Omer M, Chait A. 10E-12Z-conjugated linoleic acid impairs adipocyte triglyceride storage by enhancing fatty acid oxidation, lipolysis, and mitochondrial reactive oxygen species. J Lipid Res 2013 Aug 17. [Epub ahead of print].
den Hartigh LJ, Altman R, Hutchinson R, Petrlova J, Budamagunta MS, Tetali SD, Lagerstedt JO, Voss JC, Rutledge JC. Postprandial apoE isoform and conformational changes associated with VLDL lipolysis products modulate monocyte inflammation. PLoS ONE 2012; 7(11): e50513.
Han CY, Umemoto T, Omer M, den Hartigh LJ, Chiba T, Leboeuf R, Buller CL, Sweet IR, Pennathur S, Abel ED, Chait A. NADPH oxidase-derived reactive oxygen species increases expression of monocyte chemotactic factor genes in cultured adipocytes. J Biol Chem 2012 Mar 23; 287(13):10379-93.
den Hartigh LJ, Connolly-Rohrbach JE, Fore S, Huser T, Rutledge JC. Fatty acids from VLDL lipolysis products induce lipid droplet accumulation in human monocytes. J Immunol 2010 April 1; 184(7):3927-36.
Higgins LJ, Rutledge JC. Inflammation associated with the postprandial lipolysis of triglyceride-rich lipoproteins by lipoprotein lipase. Curr Atheroscler Rep 2009 May; 11(3):199-205.
Averill MM, Kim EJ, Goodspeed L, Wang S, Subramanian S, den Hartigh LJ, Tang C, Ding Y, Reardon CA, Getz GS, Chait A (2014). The Apolipoprotein-AI Mimetic Peptide L4F at a Modest Dose Does Not Attenuate Weight Gain, Inflammation, or Atherosclerosis in LDLR-Null Mice. PLoS One. Oct 6;9(10):e109252.
Rubinow KB, Wang S, den Hartigh LJ, Subramanian S, Morton GJ, Buaas FW, Lamont D, Gray N, Braun RE, Page ST (2015). Hematopoietic androgen receptor deficiency promotes visceral fat deposition in male mice without impairing glucose homeostasis. Andrology. 2015 Jul;3(4):787-96.
den Hartigh LJ, Altman R, Norman JE, Rutledge JC (2013). Postprandial VLDL lipolysis products increase monocyte adhesion and lipid droplet formation via activation of ERK2 and NFκB. Am J Physiol Heart Circ 2013 Oct 25. 2014 Jan 1;306(1):H109-20.
Montes VN, Turner MS, Subramanian S, Ding Y, Hayden-Ledbetter M, Slater S, Goodspeed L, Wang S, Omer M, den Hartigh LJ, Averill MM, O’Brien KD, Ledbetter J, Chait A (2013). T cell activation inhibitors reduce CD8+ T cell and pro-inflammatory macrophage accumulation in adipose tissue of obese mice. PLoS ONE 2013 Jul 2;8(7):e67709.
Umemoto T, Han CY, Mitra P, Averill MM, Tang C, Goodspeed L, Omer M, Subramanian S, Wang S, den Hartigh LJ, Kim EJ, Kim J, O’Brien KD, Chait A. Apolipoprotein A-I and HDL have anti-inflammatory effects on adipocyte inflammation via cholesterol transporters; ATP-binding cassette (ABC) A-1, ABCG-1 and scavenger receptor B-1(SRB-1). Circ Res 2013 Mar 15.
Tablin F, den Hartigh LJ, Aung HH, Lame MW, Kleeman MJ, Ham W, Norris JW, Pombo M, Wilson DW. Seasonal influences on CAPs exposures: Differential responses in platelet activation, serum cytokines, and xenobiotic expression. Inhal Toxicol 2012 Jul;24(8):506-17.
Weeks T, Schie I, den Hartigh LJ, Rutledge JC, Huser T. Lipid-cell interactions in human monocytes investigated by doubly-resonant coherent anti-Stokes Raman (DR-CARS) microscopy. Journal of Biomedical Optics (2011) Feb;16(2):021117.
den Hartigh LJ, Lame MW, Tablin F, Wilson DW. Endotoxin and polycyclic aromatic hydrocarbons in ambient fine particulate matter from Fresno, California initiate human monocyte inflammatory responses mediated by reactive oxygen species. Toxicology in Vitro 2010; 24 1993–2002.
Tetali SD, Budamagunta MS, Simion C, den Hartigh LJ, Kalai T, Hideg K, Hatters DM, Weisgraber KH, Voss JC, Rutledge JC. VLDL lipolysis products increase VLDL fluidity and convert apolipoprotein E4 into a more expanded conformation. J Lipid Res 2010 Jun;51(6):1273-83.
Wang L, Gill R, Pederson TL, Higgins LJ, Newman JW, Rutledge JC. Triglyceride-rich lipoprotein lipolysis releases neutral and oxidized FFAs that induce endothelial inflammation. J Lipid Res 2009 Feb; 50(2):204-13.
Within the Diabetes and Obesity Center of Excellence and its Affiliated Members
Alan Chait, MD
Chang Yeop Han, MD
Gregory Morton, PhD
Daniel Raftery, PhD,
Savitha Subramanian, MD
Outside of the Diabetes and Obesity Center of Excellence
Kevin O’Brien, MD, University of Washington
Catherine Reardon, PhD, University of Chicago