Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 28, 2018; 24(4): 461-474
Published online Jan 28, 2018. doi: 10.3748/wjg.v24.i4.461
Diet switch and omega-3 hydroxy-fatty acids display differential hepatoprotective effects in an obesity/nonalcoholic fatty liver disease model in mice
Roberto Rodriguez-Echevarria, Jose Macias-Barragan, Marcela Parra-Vargas, Judith Rebeca Davila-Rodriguez, Eduardo Amezcua-Galvez, Juan Armendariz-Borunda
Roberto Rodriguez-Echevarria, Marcela Parra-Vargas, Juan Armendariz-Borunda, Institute for Molecular Biology and Gene Therapy-CUCS, Department of Molecular Biology and Genomics, University of Guadalajara, Guadalajara 44340, Mexico
Jose Macias-Barragan, Department of Health Sciences-CUValles, University of Guadalajara, Guadalajara 46600, Mexico
Judith Rebeca Davila-Rodriguez, Eduardo Amezcua-Galvez, Hospital Civil de Guadalajara, Guadalajara 46600, Mexico
Author contributions: Rodriguez-Echevarria R and Armendariz-Borunda J designed the study; Armendariz-Borunda J and Macias-Barragan J contributed with data analysis, direction and guidance; Rodriguez-Echevarria R and Parra-Vargas M developed the methodology, collected the data and performed data analysis; Davila-Rodriguez JR, and Amezcua-Galvez E performed alpha-SMA immunohistochemistry; Rodriguez-Echevarria R and Armendariz-Borunda J wrote the manuscript.
Institutional animal care and use committee statement: This research protocol was approved by the CUCS Research Committee from Universidad de Guadalajara. Also, it was carried out in accordance with the National Institutes of Health guide for care and use of laboratory animals.
Conflict-of-interest statement: The authors of this manuscript declare no conflict of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Juan Armendariz-Borunda, PhD, Professor, FAASLD, Head, Institute for Molecular Biology and Gene Therapy CUCS, Department of Molecular Biology and Genomics, University of Guadalajara, 950 Sierra Mojada St., Guadalajara 44340, Mexico. armdbo@gmail.com
Telephone: +52-33-1058 5200
Received: September 11, 2017
Peer-review started: September 12, 2017
First decision: October 18, 2017
Revised: November 22, 2017
Accepted: November 28, 2017
Article in press: November 28, 2017
Published online: January 28, 2018
Processing time: 136 Days and 11.8 Hours
Abstract
AIM

To study the effect of 18-hydroxy-eicosapentaenoic acid (18-HEPE) and 17-hydroxy-docosahexaenoic acid (17-HDHA) in a murine model of obesity/nonalcoholic fatty liver disease.

METHODS

C57BL/6 mice were fed with standard chow diet (CD) or high-fat, fructose-enriched diet (HFD) for 16 wk. Then, three groups were treated for 14 d with either, diet switch (HFD for CD), 18-HEPE, or 17-HDHA. Weight and fasting glucose were recorded on a weekly basis. Insulin tolerance test was performed at the end of treatment. Histological analysis (HE and Masson’s trichrome stain) and determination of serum insulin, glucagon, glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide, adiponectin and resistin were carried out as well as liver proteins by western blot.

RESULTS

Mice treated with hydroxy-fatty acids 18-HEPE and 17-HDHA displayed no weight loss or improved insulin sensitivity. However, these mice groups showed a significant amelioration on serum GLP-1, adiponectin and resistin levels. Also, a significant reduction on inflammatory infiltrate was observed at both portal and lobular zones. Furthermore, up-regulation of PPARα/γ protein levels was observed in liver tissue and it was associated with decreased levels of NF-κB also determined by western blot analysis. On the other hand, diet switch regimen resulted in a marked improvement in most parameters including: weight loss, increased insulin sensitivity, decreased steatosis, restored levels of insulin, glucagon, leptin, adiponectin and resistin. However, no significant changes were observed regarding inflammatory infiltrate in this last group.

CONCLUSION

18-HEPE and 17-HDHA differentially exert hepatoprotective effects through up-regulation of nuclear receptors PPARα/γ and amelioration of serum adipokines profile.

Keywords: Nonalcoholic fatty liver disease; Polyunsaturated fatty acids; 18-hydroxy-eicosapentaenoic acid; 17-hydroxy-docosahexaenoic acid; Obesity

Core tip: Our study aimed to prove the efficacy of hydroxy-fatty acids 18-hydroxy-eicosapentaenoic acid and 17-hydroxy-docosahexaenoic acid (17-HDHA) in an obesity/nonalcoholic fatty liver disease (NAFLD) model in mice. We determined the effect of these molecules on histological morphology as well as in protein levels of key nuclear receptors and serum hormones, incretins and adipokines as these parameters are altered in NAFLD. We reported an effect by these hydroxy-fatty acids on the most relevant target proteins involved in this pathological process (PPARα/γ). Also, we demonstrated that diet switch regimen is a selective treatment control as most NAFLD markers and histological alterations were ameliorated by this intervention.