Next Article in Journal
The Impact of Intermittent Fasting (Ramadan Fasting) on Psoriatic Arthritis Disease Activity, Enthesitis, and Dactylitis: A Multicentre Study
Previous Article in Journal
Serum Concentration of Genistein, Luteolin and Colorectal Cancer Prognosis
Article Menu
Issue 3 (March) cover image

Export Article

Open AccessArticle

Eicosapentaenoic Acid Improves Hepatic Metabolism and Reduces Inflammation Independent of Obesity in High-Fat-Fed Mice and in HepG2 Cells

1
Department of Nutritional Sciences and Obesity Research Cluster, Texas Tech University, Lubbock, TX 79409, USA
2
Department of Physiology, University of Peradeniya, 20400 Peradeniya, Sri Lanka
*
Author to whom correspondence should be addressed.
Nutrients 2019, 11(3), 599; https://doi.org/10.3390/nu11030599
Received: 29 January 2019 / Revised: 5 March 2019 / Accepted: 6 March 2019 / Published: 12 March 2019
  |  
PDF [3310 KB, uploaded 12 March 2019]
  |  

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. View Full-Text
Keywords: eicosapentaenoic acid; inflammation; nonalcoholic fatty liver disease; obesity; omega-3 polyunsaturated fatty acids eicosapentaenoic acid; inflammation; nonalcoholic fatty liver disease; obesity; omega-3 polyunsaturated fatty acids
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Albracht-Schulte, K.; Gonzalez, S.; Jackson, A.; Wilson, S.; Ramalingam, L.; Kalupahana, N.S.; Moustaid-Moussa, N. Eicosapentaenoic Acid Improves Hepatic Metabolism and Reduces Inflammation Independent of Obesity in High-Fat-Fed Mice and in HepG2 Cells. Nutrients 2019, 11, 599.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Nutrients EISSN 2072-6643 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top