Polyunsaturated fatty acids of marine origin upregulate mitochondrial biogenesis and induce β-oxidation in white fat
Open accessAbstract
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.
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Some anti-obesity effects of PUFAs could be independent of UCP-1-dependent mitochondrial uncoupling.
“Importantly, we must note that some anti-obesity effects of PUFAs could be independent of UCP-1-dependent mitochondrial uncoupling.”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [286]
Although HFD supplemented with n-3 PUFA protects C57BL/6J mice against weight gain, no effect on expression and/or activation of UCP-1 could be found.
“Indeed, although HFD supplemented with n-3 PUFA protects C57BL/6J mice against weight gain, no effect on the expression and/or activation of the gene encoding the thermogenic UCP-1 could be found [286].”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [286]
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- Authors
- Flachs, P., Horakova, O., Brauner, P., Rossmeisl, M., Pecina, P., Franssen-van Hal, N., Ruzickova, J., Sponarova, J., Drahota, Z., Vlcek, C., Keijer, J., Houstek, J., & Kopecky, J.
- Affiliations
- Czech Academy of Sciences (CZ)
- Wageningen University & Research (NL)
- Venue
- Diabetologia
- Published
- 2005-10-05
- Volume
- 48
- Issue
- 11
- Pages
- 2365-2375
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2126272143
- Cited by
- 388
- References
- 51
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 12 · 2023: 11 · 2022: 10 · 2021: 13 · 2020: 25 · 2019: 23 · 2018: 22 · 2017: 12 · 2016: 26 · 2015: 30 · 2014: 28 · 2013: 34 · 2012: 19
- FWCI
- 14.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Socio-Environmental Systems Modeling (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Ministerstvo Školství, Mládeže a Tělovýchovy (AVOZ50110509, 1 M6837805002)
- Grantová Agentura České Republiky (1M6837805002, 50110509, AVOZ 50110509)
- Advanced Scientific Computing Research
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- omega-3 fatty acids, eicosapentaenoic acid, docosahexaenoic acid, mitochondrial biogenesis, fatty acid beta-oxidation, white adipose tissue, epididymal adipose tissue, PGC-1α, NRF1, CPT1A, lipogenesis, obesity, high-fat diet, adipocyte gene expression
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Adipose Tissue, Animals, Carnitine O-Palmitoyltransferase, Cells, Cultured, Docosahexaenoic Acids, Epididymis, Fatty Acids, Unsaturated, Fish Oils, Gene Expression Regulation, Male, Mice, Inbred C57BL, Mitochondria, Obesity, Oxidation-Reduction, Transcription Factors, Eicosapentaenoic Acid, Trans-Activators, Adipocytes, alpha-Linolenic Acid, Mitochondrial Proteins, Subcutaneous Fat, Lipogenesis, NF-E2-Related Factor 1, Mice
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