Eicosapentaenoic Acid Improves Hepatic Metabolism and Reduces Inflammation Independent of Obesity in High-Fat-Fed Mice and in HepG2 Cells
Albracht-Schulte K, Gonzalez S, Jackson A, Wilson S, Ramalingam L, Kalupahana NS, Moustaid-Moussa N
Nutrients · 44 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- Animal study (classified by our AI screen)
- Studied in
- People, plus animal or lab work
- Main outcome
- Mechanisms only
Who paid for it
- Funding
- Independent funding
- Government
- U.S. Department of Agriculture
- Nonprofit
- American Heart Association
- University or hospital
- Texas Tech University
- Government
- National Institutes of Health
- Government
- National Institute of Food and Agriculture
- Government
- National Center for Complementary and Integrative Health
- Government
- NCCIH NIH HHS
- Government
- NIH HHS
- Grants
- U.S. Department of Agriculture (2017-67011-26029); National Institutes of Health (1r15at008879-01a1); National Center for Complementary and Integrative Health (R15 AT008879)
Based on 8 listed funder(s).
Publication
- Published
- 2019-03-12 · Nutrients · vol. 11 · issue 3 · p. 599
- Publisher
- Multidisciplinary Digital Publishing Institute
- Cited
- 60 citations · more than 96% of similar papers · 4.9× the field average
- Impact
- Top 10% most cited in its field
- References
- 70 works
- Access
- Open access (journal) · CC-BY
- Research areas
- Liver Disease Diagnosis and Treatment · Peroxisome Proliferator-Activated Receptors · Diet, Metabolism, and Disease
- Keywords
- Eicosapentaenoic acid, Steatosis, Endocrinology, Internal medicine, Fatty acid synthase, Biology, Lipid metabolism, Polyunsaturated fatty acid, Nonalcoholic fatty liver disease, Fatty liver, CD36, Inflammation, Fatty acid metabolism, Fatty acid, Metabolism, Medicine, Biochemistry, Receptor
- MeSH
- liver, animals, mice, inbred c57bl, humans, mice, obesity, eicosapentaenoic acid, fatty acids, micrornas, gene expression regulation, lipid peroxidation, male, lipid metabolism, hep g2 cells, diet, high-fat
7 authors
From US, LK
- Kembra Albracht‐SchulteTexas Tech University
- Samantha GonzalezTexas Tech University
- Abigail JacksonTexas Tech University
- Savanna WilsonTexas Tech University
- Latha RamalingamTexas Tech University
- Nishan S. KalupahanaUniversity of Peradeniya; Texas Tech University
Abstract
The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide, concurrent with increased obesity. Thus, there is urgent need for research that can lead to effective NAFLD prevention/treatment strategies. Omega-3 polyunsaturated fatty acids (n-3 PUFAs), including eicosapentaenoic acid (EPA), improve inflammation- and dyslipidemia-related metabolic disorders; however, mechanisms mediating the benefits of n-3 PUFAs in NAFLD treatment are less understood. We previously reported that EPA reversed obesity-induced hepatic steatosis in high-fat (HF)-fed B6 mice. Utilizing a combination of biochemical analyses of liver tissues from HF and HF-EPA-fed mice and a series of in vitro studies in tumor necrosis factor-alpha (TNF-α)-stimulated HepG2 cells, we dissect the mechanistic effects of EPA in reducing hepatic steatosis, including the role of EPA-targeted microRNAs (miRNA). With EPA, hepatic lipid metabolism was improved in HF-EPA mice, as indicated by decreased protein and messenger RNA (mRNA) levels of fatty acid synthase (FASN) and acetyl-CoA carboxylase (Acaca) gene, and increased mRNA levels for the peroxisome proliferator activated receptor-α (Pparα), and carnitine palmitoyltransferase (Cpt) 1a and 2 genes in the HF-EPA mice. Additionally, inflammation was reduced, as shown by decreased tumor necrosis factor-alpha (Tnfα) gene expression. Accordingly, EPA also significantly reduced FASN and ACACA mRNAs in human HepG2 cells. Glycolysis, estimated by extracellular acidification rate, was significantly reduced in HepG2 cells treated with EPA vs. vehicle. Furthermore, we identified several miRNAs that are regulated by EPA in mouse liver, including miR-19b-3p, miR-21a-5p, and others, which target lipid metabolism and inflammatory pathways. In conclusion, our findings provide novel mechanistic evidence for beneficial effects of EPA in NAFLD, through the identification of specific genes and miRNAs, which may be further exploited as future NAFLD therapies.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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