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

Joao A G Duarte, Filipa Carvalho, Mackenzie Pearson, Jay D. Horton, Jeffrey D. Browning, John G. Jones, Shawn C. Burgess

Research output: Contribution to journalArticle

53 Citations (Scopus)

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.

Original languageEnglish (US)
Article numberA11
Pages (from-to)2541-2553
Number of pages13
JournalJournal of Lipid Research
Volume55
Issue number12
DOIs
StatePublished - Jan 1 2015

Fingerprint

Lipogenesis
High Fat Diet
Nutrition
Elongation
Triglycerides
Fats
Lipids
Glycerides
Obesity
Nuclear magnetic resonance
Fluxes
Liver
Fat-Restricted Diet
Deuterium
Fatty Liver
Isotopes
Glycerol
Insulin Resistance
Hydrogen
Pharmacology

Keywords

  • Adipose
  • Lipid metabolism
  • Lipidomics
  • Liver
  • Nuclear magnetic resonance
  • Obesity

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Endocrinology

Cite this

A high-fat diet suppresses de novo lipogenesis and desaturation but not elongation and triglyceride synthesis in mice. / Duarte, Joao A G; Carvalho, Filipa; Pearson, Mackenzie; Horton, Jay D.; Browning, Jeffrey D.; Jones, John G.; Burgess, Shawn C.

In: Journal of Lipid Research, Vol. 55, No. 12, A11, 01.01.2015, p. 2541-2553.

Research output: Contribution to journalArticle

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