Eicosapentaenoic acid promotes mitochondrial biogenesis and beige-like features in subcutaneous adipocytes from overweight subjects
Abstract
Eicosapentaenoic acid (EPA), a n-3 long-chain polyunsaturated fatty acid, has been reported to have beneficial effects in obesity-associated metabolic disorders. The objective of the present study was to determine the effects of EPA on the regulation of genes involved in lipid metabolism, and the ability of EPA to induce mitochondrial biogenesis and beiging in subcutaneous adipocytes from overweight subjects. Fully differentiated human subcutaneous adipocytes from overweight females (BMI: 28.1-29.8kg/m 2) were treated with EPA (100-200 μM) for 24 h. Changes in mRNA expression levels of genes involved in lipogenesis, fatty acid oxidation and mitochondrial biogenesis were determined by qRT-PCR. Mitochondrial content was evaluated using MitoTracker® Green stain. The effects on peroxisome proliferator-activated receptor gamma, co-activator 1 alpha (PGC-1α) and AMP-activated protein kinase (AMPK) were also characterized. EPA down-regulated lipogenic genes expression while up-regulated genes involved in fatty acid oxidation. Moreover, EPA-treated adipocytes showed increased mitochondrial content, accompanied by an up-regulation of nuclear respiratory factor-1, mitochondrial transcription factor A and cytochrome c oxidase IV mRNA expression. EPA also promoted the activation of master regulators of mitochondrial biogenesis such as sirtuin 1, PGC1-α and AMPK. In parallel, EPA induced the expression of genes that typify beige adipocytes such as fat determination factor PR domain containing 16, uncoupling protein 1 and cell death-inducing DFFA-like effector A, T-Box protein 1 and CD137. Our results suggest that EPA induces a remodeling of adipocyte metabolism preventing fat storage and promoting fatty acid oxidation, mitochondrial biogenesis and beige-like markers in human subcutaneous adipocytes from overweight subjects.
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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 [71]
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- Authors
- Laiglesia, L. M., Lorente-Cebrián, S., Prieto-Hontoria, P. L., Fernández-Galilea, M., Ribeiro, S. M. R., Sáinz, N., Martínez, J. A., & Moreno-Aliaga, M. J.
- Affiliations
- Universidad de Navarra (ES)
- Universidade Federal de Viçosa (BR)
- Instituto de Salud Carlos III (ES)
- Corresponding author
- Moreno-Aliaga, M.J.
- Venue
- The Journal of Nutritional Biochemistry
- Publisher
- Elsevier BV
- Published
- 2016-11
- Volume
- 37
- Pages
- 76-82
- ISSN
- 0955-2863 (ISSN-L)
- OpenAlex
- W2517909381
- Cited by
- 85
- References
- 59
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 9 · 2023: 9 · 2022: 9 · 2021: 6 · 2020: 16 · 2019: 9 · 2018: 13 · 2017: 6
- FWCI
- 7.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Nutritional Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Asociación de Amigos de la Universidad de Navarra
- 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 › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- eicosapentaenoic acid, omega-3 fatty acids, mitochondrial biogenesis, adipocyte browning, beige adipocytes, subcutaneous adipocytes, overweight, obesity, fatty acid oxidation, lipogenesis, PGC-1α, AMPK, SIRT1, UCP1, 4-1BB, adipocyte metabolism
- MeSH terms
- Adipocytes, Beige, Organelle Biogenesis, Carnitine O-Palmitoyltransferase, Cells, Cultured, Energy Metabolism, Female, Humans, Osmolar Concentration, Stearoyl-CoA Desaturase, Eicosapentaenoic Acid, Biomarkers, Gene Expression Regulation, Enzymologic, Body Mass Index, Acyl-CoA Oxidase, Adipogenesis, Lipid Metabolism, Subcutaneous Fat, Abdominal, Diacylglycerol O-Acyltransferase, Adipocytes, White, Mitochondrial Dynamics, Fatty Acid Synthases
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