A high-fat diet suppresses de novo lipogenesis and desaturation but not elongation and triglyceride synthesis in mice

被引:147
作者
Duarte, Joao A. G. [1 ,4 ]
Carvalho, Filipa [4 ]
Pearson, Mackenzie [1 ]
Horton, Jay D. [2 ]
Browning, Jeffrey D. [1 ,2 ]
Jones, John G. [4 ]
Burgess, Shawn C. [1 ,3 ]
机构
[1] Univ Texas SW Med Ctr Dallas, Adv Imaging Res Ctr, Div Metab Mechanisms Dis, Dallas, TX 75390 USA
[2] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA
[3] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA
[4] Univ Coimbra, Ctr Neurosci & Cell Biol, Dept Zool, Coimbra, Portugal
基金
美国国家卫生研究院;
关键词
lipid metabolism; obesity; liver; adipose; nuclear magnetic resonance; lipidomics; ISOTOPOMER DISTRIBUTION ANALYSIS; CULTURED RAT HEPATOCYTES; HEPATIC LIPID-METABOLISM; INSULIN-RESISTANCE; CHOLESTEROL-SYNTHESIS; INDUCED OBESITY; ACID SYNTHESIS; LIVER-DISEASE; PATHWAY; GLUCONEOGENESIS;
D O I
10.1194/jlr.M052308
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Intracellular lipids and their synthesis contribute to the mechanisms and complications of obesity-associated diseases. We describe an NMR approach that provides an abbreviated lipidomic analysis with concurrent lipid biosynthetic fluxes. Following deuterated water administration, positional isotopomer analysis by deuterium NMR of specific lipid species was used to examine flux through de novo lipogenesis (DNL), FA elongation, desaturation, and TG-glycerol synthesis. The NMR method obviated certain assumptions regarding sites of enrichment and exchangeable hydrogens required by mass isotope methods. The approach was responsive to genetic and pharmacological gain or loss of function of DNL, elongation, desaturation, and glyceride synthesis. BDF1 mice consuming a high-fat diet (HFD) or matched low-fat diet for 35 weeks were examined across feeding periods to determine how flux through these pathways contributes to diet induced fatty liver and obesity. HFD mice had increased rates of FA elongation and glyceride synthesis. However DNL was markedly suppressed despite insulin resistance and obesity. We conclude that most hepatic TGs in the liver of HFD mice were formed from the reesterification of existing or ingested lipids, not DNL.
引用
收藏
页码:2541 / 2553
页数:13
相关论文
共 55 条
[1]   Acetyl-CoA Carboxylase 2-/- Mutant Mice are Protected against Fatty Liver under High-fat, High-carbohydrate Dietary and de Novo Lipogenic Conditions [J].
Abu-Elheiga, Lutfi ;
Wu, Hongmei ;
Gu, Ziwei ;
Bressler, Rubin ;
Wakil, Salih J. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287 (15) :12578-12588
[2]   Triglyceride Synthesis in Epididymal Adipose Tissue CONTRIBUTION OF GLUCOSE AND NON-GLUCOSE CARBON SOURCES [J].
Bederman, Ilya R. ;
Foy, Steven ;
Chandramouli, Visvanathan ;
Alexander, James C. ;
Previs, Stephen F. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (10) :6101-6108
[3]   Influence of diet on the modeling of adipose tissue triglycerides during growth [J].
Brunengraber, DZ ;
McCabe, BJ ;
Kasumov, T ;
Alexander, JC ;
Chandramouli, V ;
Previs, SF .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2003, 285 (04) :E917-E925
[4]  
Burr G, 1932, J BIOL CHEM, V97, P1
[5]   Noninvasive Measurement of Murine Hepatic Acetyl-CoA 13C-Enrichment Following Overnight Feeding with 13C-Enriched Fructose and Glucose [J].
Carvalho, Filipa ;
Duarte, Joao ;
Simoes, Ana Rita ;
Cruz, Pedro F. ;
Jones, John G. .
BIOMED RESEARCH INTERNATIONAL, 2013, 2013
[6]   Identifying Static and Kinetic Lipid Phenotypes by High Resolution UPLC-MS: Unraveling Diet-Induced Changes in Lipid Homeostasis by Coupling Metabolomics and Fluxomics [J].
Castro-Perez, Jose M. ;
Roddy, Thomas P. ;
Shah, Vinit ;
McLaren, David G. ;
Wang, Sheng-Ping ;
Jensen, Kristian ;
Vreeken, Rob J. ;
Hankemeier, Thomas ;
Johns, Douglas G. ;
Previs, Stephen F. ;
Hubbard, Brian K. .
JOURNAL OF PROTEOME RESEARCH, 2011, 10 (09) :4281-4290
[7]   Physiologic and Pharmacologic factors influencing glyceroneogenic contribution to triacylglyceride glycerol measured by mass isotopomer distribution analysis [J].
Chen, JL ;
Peacock, E ;
Samady, W ;
Turner, SM ;
Neese, RA ;
Hellerstein, MK ;
Murphy, EJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (27) :25396-25402
[8]   Sources of hepatic triglyceride accumulation during high-fat feeding in the healthy rat [J].
Delgado, T. C. ;
Pinheiro, D. ;
Caldeira, M. ;
Castro, M. M. C. A. ;
Geraldes, C. F. G. C. ;
Lopez-Larrubia, P. ;
Cerdan, S. ;
Jones, J. G. .
NMR IN BIOMEDICINE, 2009, 22 (03) :310-317
[9]  
Diraison F, 1997, J MASS SPECTROM, V32, P81, DOI 10.1002/(SICI)1096-9888(199701)32:1<81::AID-JMS454>3.0.CO
[10]  
2-2