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 alpha-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 alpha-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 Pgc1alpha] 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 beta-oxidation and upregulation of mitochondrial biogenesis.

• MeSH
• epididymis účinky léků   metabolismus   MeSH
• faktor 1 související s NF-E2 účinky léků   genetika   MeSH
• karnitin-O-palmitoyltransferasa účinky léků   genetika   MeSH
• kultivované buňky MeSH
• kyselina alfa-linolenová farmakologie   MeSH
• kyselina eikosapentaenová farmakologie   MeSH
• kyseliny dokosahexaenové farmakologie   MeSH
• lipogeneze účinky léků   MeSH
• mitochondriální proteiny účinky léků   metabolismus   MeSH
• mitochondrie účinky léků   metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nenasycené mastné kyseliny izolace a purifikace   metabolismus   farmakologie   MeSH
• obezita prevence a kontrola   MeSH
• oxidace-redukce MeSH
• podkožní tuk účinky léků   metabolismus   MeSH
• PPARGC1A MeSH
• regulace genové exprese účinky léků   MeSH
• rybí oleje chemie   MeSH
• trans-aktivátory účinky léků   genetika   MeSH
• transkripční faktory MeSH
• tuková tkáň účinky léků   metabolismus   MeSH
• tukové buňky účinky léků   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• faktor 1 související s NF-E2 MeSH
• karnitin-O-palmitoyltransferasa MeSH
• kyselina alfa-linolenová MeSH
• kyselina eikosapentaenová MeSH
• kyseliny dokosahexaenové MeSH
• mitochondriální proteiny MeSH
• nenasycené mastné kyseliny MeSH
• Ppargc1a protein, mouse MeSH Prohlížeč
• PPARGC1A MeSH
• rybí oleje MeSH
• trans-aktivátory MeSH
• transkripční faktory MeSH