Mammalian physiology requires extraordinary metabolic flexibility in order to adapt to variations in nutrient availability and energy requirements. This regulation is executed through hormone signaling, enzyme expression/modification and substrate level factors that act in concert for the ultimate purpose of controlling biochemical flux through specific metabolic pathways. Ultimately, it is the dysregulation of flux through metabolic networks that triggers the manifestation of disease. The Burgess lab uses Nuclear Magnetic Resonance spectroscopy and mass spectrometry in conjunction with the application of stable isotope (non-radioactive) tracers to study metabolic function. These approaches are applied in combination with standard molecular biological and biochemical methods in gene altered animal models and isolated cells to study the metabolic basis of disease. We focus mainly on pathways of lipid and carbohydrate metabolism in liver, kidney and a-cell in the context of obesity, insulin resistance and diabetes or in models with specific interventions in hepatic energy and carbohydrate metabolism. Both the technologies and metabolic insight from these studies are translated towards the understanding of human physiology by partnering with clinical scientists to study human subjects. Our goal is to use cross-disciplinary approaches to provide a clear understanding of how molecular biology influences metabolic function in physiology and disease.
RESEARCH INTERESTS
Biological NMR methods
Intermediary metabolism: Elucidation of metabolic pathways
In Vivo and Ex Vivo isotope tracer techniques
Metabolism in animal models of diabetes and obesity
RECENT PUBLICATIONS
Shawn C Burgess, Merrill Nuss, Bernard R Landau, A Dean Sherry and Craig R Malloy, "Comparison of 2H2O Measured Gluconeogenesis Determined by Both NMR and MS" Analytical Biochemistry, 318:321-324, 2003
Inagaki T, Dutchak P, Zhao G, Ding X, Gautron L, Parameswara V, Li Y, Goetz R, Mohammad M, Esser V, Elmquist JK, Gerard RD, Burgess SC, Hammer RE, Mangelsdorf DJ, Kliewer SA, "Regulation of the Fasting Response by PPARa-Mediated Induction of Fibroblast Growth Factor 21" Cell Metabolism, IN PRESS 2007
Browning JD, Davis J, Saboorian MH, and Burgess SC, "A low-carbohydrate diet rapidly and dramatically reduces intrahepatic triglyceride content. Hepatology" Hepatology, 44:487-488, 2006
Natasha Hausler, Matthew Merritt, Charles Storey, Angela Milde, A. Dean Sherry Craig R. Malloy and SC Burgess, "Effects of Insulin and Cytosolic Redox State on Glucose Production Pathways in the Isolated Perfused Mouse Liver by Integrated 2H and 13C NMR" Biochemical Journal, 395:663, 2006
S. Satapati, TT. He, T. Inagaki, M. Potthoff, ME. Merritt, V. Esser, DJ. Mangelsdorf, SA Kliewer, JD. Browning and SC. Burgess, "Partial Resistance to PPAR-alpha Agonists in ZDF Rats is Associated with Defective Hepatic Mitochondrial Metabolism" Diabetes, 57:2012-2021, August 2008
SIGNIFICANT PUBLICATIONS
Danhong Lu, Hindrik Mulder, Piyu Zhao, Shawn C Burgess, Mette V Jensen, Svetlana Kamzolova, Christopher B Newgard and A Dean Sherry, "13C NMR Isotopomer Analysis Reveals a Connection Between Pyruvate Cycling and Glucose-Stimulated Insulin Secretion (GSIS)" PNAS, 99:2708-2713, 2002
Pengxiang She, Shawn C. Burgess, Masakazu Shiota, Paul Flakoll, E Patrick Donahue, Craig R Malloy, A Dean Sherry, and Mark A Magnuson, "Mechanisms by which liver-specific PEPCK knockout mice preserve euglycemia during starvation" Diabetes, 52:1649-1654, 2003
Burgess SC, Hausler N, Merritt M, Jeffrey FMH, Storey C, Milde A, Koshy S, Lindner J, Magnuson MA, Malloy CR, and Sherry AD., "Impaired Tricarboxylic Acid Cycle Activity in Mouse Livers Lacking Cytosolic Phosphoenolpyruvate Carboxykinase" Journal of Biological Chemistry, 279:48941-48949, December 2004
Burgess SC, Leone TC, Wende AR, Croce MA, Chen Z, Sherry AD, Malloy CR, and Finck BN, "Diminished hepatic gluconeogenesis via defects in tricarboxylic acid cycle flux in peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha)-deficient mice" Journal of Biological Chemistry, 281:19000-19008, December 2004
34. Burgess SC, He T, Yan Z, Lindner J, Sherry AD, Malloy CR, Browning JD, Magnuson MA, "Cytosolic Phosphoenolpyruvate Carboxykinase Does Not Solely Control the Rate of Hepatic Gluconeogenesis in the Intact Mouse Liver" Cell Metabolism, 5:313-320, April 2007
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