title: Novel insights into obesity and diabetes through genome-scale metabolic modeling.
abstract: The growing prevalence of metabolic diseases, such as obesity and diabetes, are putting a high strain on global healthcare systems as well as increasing the demand for efficient treatment strategies. More than 360 million people worldwide are suffering from type 2 diabetes (T2D) and, with the current trends, the projection is that 10% of the global adult population will be affected by 2030. In light of the systemic properties of metabolic diseases as well as the interconnected nature of metabolism, it is necessary to begin taking a holistic approach to study these diseases. Human genome-scale metabolic models (GEMs) are topological and mathematical representations of cell metabolism and have proven to be valuable tools in the area of systems biology. Successful applications of GEMs include the process of gaining further biological and mechanistic understanding of diseases, finding potential biomarkers, and identifying new drug targets. This review will focus on the modeling of human metabolism in the field of obesity and diabetes, showing its vast range of applications of clinical importance as well as point out future challenges.
authors: Systems and Synthetic Biology, Department of Chemical and Biological Engineering, Chalmers University of Technology Gothenburg, Sweden.
authors: Leif
authors: L
authors: Väremo
authors: Intawat
authors: I
authors: Nookaew
authors: Jens
authors: J
authors: Nielsen
keywords: constraint-based modeling; diabetes; genome-scale metabolic models; metabolic networks; metabolism; obesity; systems biology; topology
references: Proc Natl Acad Sci U S A. 2008 Jul 22;105(29):9880-5
references: 18599447
references: Cell. 2012 Jul 20;150(2):389-401
references: 22817898
references: J Intern Med. 2012 Feb;271(2):131-41
references: 22142339
references: Mol Syst Biol. 2013;9:649
references: 23511207
references: Nat Biotechnol. 2013 May;31(5):419-25
references: 23455439
references: Diabetes Res Clin Pract. 2011 Dec;94(3):311-21
references: 22079683
references: PLoS Comput Biol. 2012;8(10):e1002750
references: 23133351
references: J Intern Med. 2012 Feb;271(2):142-54
references: 22142312
references: Biotechnol J. 2013 Sep;8(9):985-96
references: 23613448
references: Cell Metab. 2008 Sep;8(3):186-200
references: 18762020
references: Diabetes. 2009 Jul;58(7):1558-67
references: 19401422
references: Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1777-82
references: 17267599
references: PLoS Comput Biol. 2011 Nov;7(11):e1002223
references: 22072950
references: PLoS Comput Biol. 2010 Apr 01;6(4):e1000729
references: 20369014
references: Am J Clin Nutr. 2011 Dec;94(6):1399-409
references: 22030226
references: J Biol Chem. 2005 Mar 25;280(12):11683-95
references: 15572364
references: PLoS Comput Biol. 2008 May 16;4(5):e1000082
references: 18483554
references: Bioinformatics. 2010 Jun 15;26(12):i255-60
references: 20529914
references: Diabetes Metab Res Rev. 2001 Sep-Oct;17(5):330-46
references: 11747139
references: PLoS Comput Biol. 2012;8(5):e1002518
references: 22615553
references: Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):2685-9
references: 15710883
references: Mol Syst Biol. 2009;5:263
references: 19401675
references: Nat Biotechnol. 2010 Dec;28(12):1248-50
references: 21139605
references: Front Physiol. 2012 Aug 06;3:299
references: 22934050
references: Mol Syst Biol. 2007;3:135
references: 17882155
references: PLoS Comput Biol. 2010 Jul 15;6(7):e1000859
references: 20657658
references: Nucleic Acids Res. 2012 Jan;40(Database issue):D109-14
references: 22080510
references: Clin Cancer Res. 2012 Oct 15;18(20):5572-84
references: 23071359
references: Nature. 2012 May 17;485(7398):S2-3
references: 22616094
references: J Biol Chem. 1999 Jun 18;274(25):17410-6
references: 10364169
references: Nat Biotechnol. 2008 Sep;26(9):1003-10
references: 18711341
references: Nat Rev Endocrinol. 2011 Nov 08;8(4):228-36
references: 22064493
references: PLoS Comput Biol. 2010 Feb 26;6(2):e1000692
references: 20195502
references: Annu Rev Nutr. 2005;25:391-406
references: 16011472
references: Nat Biotechnol. 2010 Dec;28(12):1279-85
references: 21102456
references: Nat Biotechnol. 2010 Mar;28(3):245-8
references: 20212490
references: BMC Bioinformatics. 2010 Jul 22;11:393
references: 20649990
references: Mol Syst Biol. 2009;5:320
references: 19888215
references: Nature. 2011 Aug 17;477(7363):225-8
references: 21849978
references: J Biol Chem. 2004 Sep 17;279(38):39532-40
references: 15205464
references: BMC Syst Biol. 2011 Oct 31;5:180
references: 22041191