Journal of Lipid Research
Volume 55, Issue 12, December 2014, Pages 2541-2553
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Research Articles
A high-fat diet suppresses de novo lipogenesis and desaturation but not elongation and triglyceride synthesis in mice[S]

https://doi.org/10.1194/jlr.M052308Get rights and content
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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.

lipid metabolism
obesity
liver
adipose
nuclear magnetic resonance
lipidomics

Cited by (0)

Support for this work was provided by National Institutes of Health Grants DK078184 (S.C.B.), DK058398 (S.C.B.), HL020948 (J.D.H), DK087977 (J.D.B), and EB015908 (Center resources), and by the Robert A. Welch Foundation (S.C.B.). J.A.G.D and J.G.J were supported by Portuguese Foundation for Science and Technology grants SFRH/BD/44294/2008 and PTDC/SAU-MET/111398/2009.

    Abbreviations:

    AMW

    average molecular weight

    ANC

    average number of carbons

    ANP

    average number of protons

    DNL

    de novo lipogenesis

    ELOVL

    elongation of very long chain fatty acids

    HFD

    high-fat diet

    LFD

    low-fat diet

    MIDA

    mass isotopomer distribution analysis

    NAFLD

    nonalcoholic fatty liver disease

    PABA

    para-amino benzoic acid

    SCD-1

    sterol-CoA desaturase 1

    SREBP-1

    sterol-regulatory element binding protein 1

    WAT

    white adipose tissue

[S]

The online version of this article (available at http://www.jlr.org) contains supplementary data in the form of eight tables and one figure.