Administration of eicosapentaenoic and docosahexaenoic acids may improve the remodeling and browning in subcutaneous white adipose tissue and thermogenic markers in brown adipose tissue in mice
Abstract
The role of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in browning and thermogenesis has not been fully elucidated. Thus, we meant to evaluate the effect of EPA and DHA, administered alone or combined, with the activation of browning markers in subcutaneous white adipose tissue (sWAT), and thermogenic markers in brown adipose tissue (BAT). C57BL/6 adult male mice received a control diet or a high-fructose diet (HFru) for eight weeks, but after the first three weeks, HFru was divided into new groups: HFru, HFru + EPA, HFru + DHA, and HFru-EPA + DHA. EPA and DHA diminished adipocyte hypertrophy, recovered markers of browning in sWAT and thermogenic factors in the BAT, and improved gene expressions linked with mitochondrial biogenesis and lipid metabolism. Importantly, EPA and DHA administrated alone showed stronger results than the combination of EPA + DHA. The results suggest that EPA and DHA might be useful as adjuvant strategies to treat metabolic-associated disorders.
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PUFAs such as EPA and DHA stimulate UCP1 expression and adaptive non-shivering or diet-induced thermogenesis in brown adipocytes, as well as browning of WAT in C57BL/6 mice, Sprague-Dawley rats, and overweight humans.
“PUFAs such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) also stimulate UCP1 expression and thus adaptive non-shivering or diet-induced thermogenesis in brown adipocytes, as well as the browning of the white adipose tissue (WAT) in C57BL/6 mice [67,68], Sprague-Dawley rats [69,70], and overweight humans [71].”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [67]
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Dietary fatty acids activate or deactivate brown and beige fat
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“reported that male B6 mice supplemented with EPA as 2% of total energy at 20 ◦C induced markers of browning and thermogenic factors in SAT [50].”
BackgroundBrown Adipose Tissue, Batokines, and Bioactive Compounds in Foods: An Update
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“Recent studies have found fructose can affect the browning of white adipose tissue (WAT), which is another mechanism of fructose-induced lipid metabolism disorders [6].”
PET/MRI-Evaluated Activation of Brown Adipose Tissue via Cold Exposure Impacts Lipid Metabolism
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“[14] examined the influence of EPA and DHA supplementation on the markers of browning in WAT, and of thermogenesis in BAT in mice fed with a high-fructose diet.”
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“In accordance with our results, the stimulatory effect of EPA and DHA on BAT specific genes in adult has been indicated in accumulative studies (Bargut et al., 2016b; Quesada-López et al., 2016; Pahlavani et al., 2017; Ghandour et al., 2018; Worsch et al., 2018; Bargut et al., 2019).”
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“BAT exhibited thermogenesis through the uncoupling of mitochondrial oxidation, which produced ATP and energy [47].”
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“…C 20 H 30 O 2 ) in mice also enhances BAT thermogenic properties, increasing PRDM16, PGC1 α , and UCP1 expression, and also promotes sWAT browning [82] and muscle NST through SERCA2b and FGF21 upregulation [83], supporting the idea that DHA and EPA could be attractive food-derived bioactive…”
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Diet-Induced Adipocyte Browning
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“Interestingly, the most potent effect was exerted by EPA itself, while DHA+EPA supplementation resulted mostly in significantly smaller gene upregulation than single EPA or DHA.”
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“Eicosapentaenoic acid and docosahexaenoic acid have the potential to stimulate the browning of white adipocytes and increase the expression levels of thermogenic markers [35–37].”
BackgroundNagagata, B. A., Mandarim‐de‐Lacerda, C. A., & Águila, M. B. (2024) · Cell Biochemistry and Function · doi:10.1002/cbf.70034
“Additionally, Mel increased Pgc1a and Ucp1 in the 3T3 ‐ L1 culture [48].”
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Alzubi, A., Lucchesi, A., Burns, J. L., Cho, C. Y., Ma, D. W. L., Robinson, L. E., & Monk, J. M. (2026) · Marine Drugs · doi:10.3390/md24050166
“EPA and DHA have also been shown to promote the browning of WAT in rodent models of obesity [128,131,132].”
- Authors
- Bargut, T. C. L., Martins, F. F., Santos, L. P., Aguila, M. B., & Mandarim-de-Lacerda, C. A.
- Affiliations
- Universidade Federal Fluminense (BR)
- Universidade do Estado do Rio de Janeiro (BR)
- ORCID
- Venue
- Molecular and Cellular Endocrinology
- Publisher
- Elsevier BV
- Published
- 2019-02
- Volume
- 482
- Pages
- 18-27
- ISSN
- 0303-7207 (ISSN-L)
- OpenAlex
- W2903848597
- Cited by
- 34
- References
- 79
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 4 · 2023: 5 · 2022: 6 · 2021: 3 · 2020: 7 · 2019: 2
- FWCI
- 2.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular and Cellular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- CNPq (302.920/2016-1, 305865/2017-0, 401001/2016-4)
- FAPERJ (E-26/202.935/2017, E-26/202.795/2017, E-26/201.683/2017)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- eicosapentaenoic acid, docosahexaenoic acid, omega-3 fatty acids, brown adipose tissue, white adipose tissue browning, thermogenesis, adipocyte hypertrophy, mitochondrial biogenesis, lipid metabolism, high-fructose diet, metabolic disorders, dietary supplementation
- MeSH terms
- Animals, Organelle Biogenesis, Adipose Tissue, Brown, Docosahexaenoic Acids, Fructose, Gene Expression Regulation, Male, Mice, Inbred C57BL, Random Allocation, Eicosapentaenoic Acid, Thermogenesis, Subcutaneous Fat, Lipid Metabolism, Mice, Adipose Tissue, White
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