Polyunsaturated fatty acids of marine origin upregulate mitochondrial biogenesis and induce-beta oxidation in white fat

P. Flachs, O. Horakova, P. Brauner, M. Rossmeisl, P. Pecina, N.L.W. van Franssen-Hal, J. Ruzickova, J. Sponarova, Z. Drahota, C. Vlcek, J. Keijer, J. Houstek, J. Kopecky

    Research output: Contribution to journalArticleAcademicpeer-review

    268 Citations (Scopus)

    Abstract

    Aims/hypothesis Intake of n-3 polyunsaturated fatty acids reduces adipose tissue mass, preferentially in the abdomen. The more pronounced effect of marine-derived eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids on adiposity, compared with their precursor -linolenic acid, may be mediated by changes in gene expression and metabolism in white fat. Methods The effects of EPA/DHA concentrate (6% EPA, 51% DHA) admixed to form two types of high-fat diet were studied in C57BL/6J mice. Oligonucleotide microarrays, cDNA PCR subtraction and quantitative real-time RT-PCR were used to characterise gene expression. Mitochondrial proteins were quantified using immunoblots. Fatty acid oxidation and synthesis were measured in adipose tissue fragments. Results Expression screens revealed upregulation of genes for mitochondrial proteins, predominantly in epididymal fat when EPA/DHA concentrate was admixed to a semisynthetic high-fat diet rich in -linolenic acid. This was associated with a three-fold stimulation of the expression of genes encoding regulatory factors for mitochondrial biogenesis and oxidative metabolism (peroxisome proliferator-activated receptor gamma coactivator 1 alpha [Ppargc1a, also known as Pgc1] and nuclear respiratory factor-1 [Nrf1] respectively). Expression of genes for carnitine palmitoyltransferase 1A and fatty acid oxidation was increased in epididymal but not subcutaneous fat. In the former depot, lipogenesis was depressed. Similar changes in adipose gene expression were detected after replacement of as little as 15% of lipids in the composite high-fat diet with EPA/DHA concentrate, while the development of obesity was reduced. The expression of Ppargc1a and Nrf1 was also stimulated by n-3 polyunsaturated fatty acids in 3T3-L1 cells. Conclusions/interpretation The anti-adipogenic effect of EPA/DHA may involve a metabolic switch in adipocytes that includes enhancement of -oxidation and upregulation of mitochondrial biogenesis
    Original languageEnglish
    Pages (from-to)2365-2375
    JournalDiabetologia
    Volume48
    Issue number11
    DOIs
    Publication statusPublished - 2005

    Keywords

    • activated protein-kinase
    • dietary fish-oil
    • adipose-tissue
    • gene-expression
    • messenger-rna
    • coactivator pgc-1-alpha
    • linolenic acid
    • cpt-i
    • obesity
    • metabolism

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