title: A high-fat diet suppresses de novo lipogenesis and desaturation but not elongation and triglyceride synthesis in mice.
abstract: 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.
authors.affiliation: Advanced Imaging Research Center-Division of Metabolic Mechanisms of Disease, The University of Texas Southwestern Medical Center, Dallas, TX Center for Neurosciences and Cell Biology, Department of Zoology, University of Coimbra, Coimbra, Portugal.
authors.forename: Joao A G
authors.initials: JA
authors.lastname: Duarte
authors.affiliation: Center for Neurosciences and Cell Biology, Department of Zoology, University of Coimbra, Coimbra, Portugal.
authors.forename: Filipa
authors.initials: F
authors.lastname: Carvalho
authors.affiliation: Advanced Imaging Research Center-Division of Metabolic Mechanisms of Disease, The University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Mackenzie
authors.initials: M
authors.lastname: Pearson
authors.affiliation: Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Jay D
authors.initials: JD
authors.lastname: Horton
authors.affiliation: Advanced Imaging Research Center-Division of Metabolic Mechanisms of Disease, The University of Texas Southwestern Medical Center, Dallas, TX Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Browning
authors.affiliation: Center for Neurosciences and Cell Biology, Department of Zoology, University of Coimbra, Coimbra, Portugal.
authors.forename: John G
authors.initials: JG
authors.lastname: Jones
authors.affiliation: Advanced Imaging Research Center-Division of Metabolic Mechanisms of Disease, The University of Texas Southwestern Medical Center, Dallas, TX Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Shawn C
authors.initials: SC
authors.lastname: Burgess
mesh_terms: D052436:Adipose Tissue, White / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D003433:Crosses, Genetic; D003903:Deuterium; D059305:Diet, High-Fat / Q000009:adverse effects*; D015536:Down-Regulation; D004951:Esterification; D044943:Fatty Acid Desaturases / Q000235:genetics / Q000378:metabolism*; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance; D050155:Lipogenesis; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D065626:Non-alcoholic Fatty Liver Disease / Q000201:enzymology / Q000209:etiology / Q000378:metabolism*; D009765:Obesity / Q000201:enzymology / Q000209:etiology / Q000378:metabolism*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; D003903:Deuterium; D044943:Fatty Acid Desaturases; D064429:Fatty Acid Synthases
keywords: adipose; lipid metabolism; lipidomics; liver; nuclear magnetic resonance; obesity