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Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Pathophysiol. May 15, 2017; 8(2): 39-50
Published online May 15, 2017. doi: 10.4291/wjgp.v8.i2.39
Embrionary way to create a fatty liver in portal hypertension
Maria-Angeles Aller, Natalia Arias, Isabel Peral, Sara García-Higarza, Jorge-Luis Arias, Jaime Arias
Maria-Angeles Aller, Isabel Peral, Jaime Arias, Department of Surgery, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain
Natalia Arias, UCL Division of Medicine, Institute for Liver and Digestive Health, London NW3 2PF, United Kingdom
Sara García-Higarza, Jorge-Luis Arias, Laboratory of Neuroscience, Department of Psychology, University of Oviedo, 33003 Asturias, Spain
Author contributions: Aller MA, Arias N and Arias J wrote the manuscript; Peral I, García-Higarza S and Arias JL contributed to the manuscript by providing intellectual input, and have participated in preparing the manuscript and approved its final version.
Supported by FICYT FC-15-GRUPIN 14-088 and Alfonso Martin Escudero Foundation.
Conflict-of-interest statement: The authors declare that there are any conflict of interest.
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: Maria-Angeles Aller, MD, PhD, Department of Surgery, School of Medicine, Complutense University of Madrid, Plaza de Ramón y Cajal s.n., 28040 Madrid, Spain. maaller@med.ucm.es
Telephone: +34-91-3941388 Fax: +34-91-3947115
Received: December 5, 2016
Peer-review started: December 7, 2016
First decision: January 16, 2017
Revised: February 3, 2017
Accepted: February 28, 2017
Article in press: March 2, 2017
Published online: May 15, 2017
Processing time: 161 Days and 7.7 Hours
Abstract

Portal hypertension in the rat by triple partial portal vein ligation produces an array of splanchnic and systemic disorders, including hepatic steatosis. In the current review these alterations are considered components of a systemic inflammatory response that would develop through three overlapping phenotypes: The neurogenic, the immune and the endocrine. These three inflammatory phenotypes could resemble the functions expressed during embryonic development of mammals. In turn, the inflammatory phenotypes would be represented in the embryo by two functional axes, that is, a coelomic-amniotic axis and a trophoblastic yolk-sac or vitelline axis. In this sense, the inflammatory response developed after triple partial portal vein ligation in the rat would integrate both functional embryonic axes on the liver interstitial space of Disse. If so, this fact would favor the successive development of steatosis, steatohepatitis and fibrosis. Firstly, these recapitulated embryonic functions would produce the evolution of liver steatosis. In this way, this fat liver could represent a yolk-sac-like in portal hypertensive rats. After that, the systemic recapitulation of these embryonic functions in experimental prehepatic portal hypertension would consequently induce a gastrulation-like response in which a hepatic wound healing reaction or fibrosis occur. In conclusion, studying the mechanisms involved in embryonic development could provide key results for a better understanding of the nonalcoholic fatty liver disease etiopathogeny.

Keywords: Inflammation; Non-alcoholic fatty liver disease; Hepatic steatosis; Extraembryonic functions; Fibrosis; Portal hypertension

Core tip: The current hypothesis proposes that the re-expression of two embryonic systemic functional axes in the rat after partial portal vein ligation produces a non-alcoholic fatty liver disease. These axes, a coelomicamniotic axis and a trophoblastic yolk-sac or vitelline axis, would then integrate in the interstitial liver space of Disse. If so, these recapitulated embryonic functions would produce firstly, the evolution of liver steatosis. In this way, this fat liver could represent a yolk-saclike in portal hypertensive rats. After that, these embryonic functions would induce a gastrulation-like response in which liver fibrosis occcur. For that reason, studying the mechanisms involved in embryonic development could provide key results for a better understanding of the non-alcoholic fatty liver disease pathophysiology.