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

J Lipid Res. 2014 Dec;55(12):2541-53. doi: 10.1194/jlr.M052308. Epub 2014 Sep 30.


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.

Keywords: adipose; lipid metabolism; lipidomics; liver; nuclear magnetic resonance; obesity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, White / enzymology
  • Adipose Tissue, White / metabolism
  • Animals
  • Crosses, Genetic
  • Deuterium
  • Diet, High-Fat / adverse effects*
  • Down-Regulation*
  • Esterification
  • Fatty Acid Desaturases / genetics
  • Fatty Acid Desaturases / metabolism*
  • Fatty Acid Synthases / genetics
  • Fatty Acid Synthases / metabolism
  • Insulin Resistance
  • Lipogenesis*
  • Liver / enzymology
  • Liver / metabolism*
  • Magnetic Resonance Spectroscopy
  • Male
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Transgenic
  • Non-alcoholic Fatty Liver Disease / enzymology
  • Non-alcoholic Fatty Liver Disease / etiology
  • Non-alcoholic Fatty Liver Disease / metabolism*
  • Obesity / enzymology
  • Obesity / etiology
  • Obesity / metabolism*
  • Sterol Regulatory Element Binding Protein 1 / genetics
  • Sterol Regulatory Element Binding Protein 1 / metabolism
  • Triglycerides / metabolism
  • Up-Regulation


  • Srebf1 protein, mouse
  • Sterol Regulatory Element Binding Protein 1
  • Triglycerides
  • Deuterium
  • Fatty Acid Desaturases
  • Fatty Acid Synthases