Repository logo
 

Lipidomic signatures discriminate subtle hepatic changes in the progression of porcine non-alcoholic steatohepatitis.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Herrera-Marcos, Luis V 
Martínez-Beamonte, Roberto 
Arnal, Carmen 
Barranquero, Cristina 
Puente-Lanzarote, Juan J 

Abstract

Recently, the development of non-alcoholic steatohepatitis (NASH) in common strains of pigs has been achieved using a diet high in saturated fat, fructose, cholesterol and cholate and deficient in choline and methionine. The aim of the present work was to characterize the hepatic and plasma lipidomic changes that accompany the progression of NASH and its reversal by switching pigs back to a chow diet. One month of this extreme steatotic diet was sufficient to induce porcine NASH. The lipidomic platform using liquid chromatography-mass spectrometry analyzed 467 lipid species. Seven hepatic phospholipids [PC(30:0), PC(32:0), PC(33:0), PC(33:1), PC(34:0), PC(34:3) and PC(36:2)] significantly discriminated the time of dietary exposure, and PC(30:0), PC(33:0), PC(33:1) and PC(34:0) showed rapid adaptation in the reversion period. Three transcripts, CS, MAT1A and SPP1, showed significant changes associated with hepatic triglycerides and PC(33:0). Plasma lipidomics revealed that these species [FA 16:0, FA 18:0, LPC(17:1), PA(40:5), PC(37:1), TG(45:0), TG(47:2) and TG(51:0)] were able to discriminate the time of dietary exposure. Among them, FA 16:0, FA 18:0, LPC(17:1) and PA(40:5) changed the trend in the reversion phase. Plasma LDL-cholesterol and IL12P40 were good parameters to study the progression of NASH, but their capacity was surpassed by hepatic [PC(33:0), PC(33:1), and PC(34:0)] or plasma lipid [FA 16:0, FA 18:0, and LPC(17:1)] species. Taken together, these lipid species can be used as biomarkers of metabolic changes in the progression and regression of NASH in this model. The lipid changes suggest that the development of NASH also affects peripheral lipid metabolism.

Description

Keywords

lipidomic, NASH, PC(33:0), PC(33:1), swine

Journal Title

American Journal of Physiology - Gastrointestinal and Liver Physiology

Conference Name

Journal ISSN

0193-1857
1522-1547

Volume Title

Publisher

American Physiological Society
Sponsorship
Biotechnology and Biological Sciences Research Council (BB/P028195/1)
Biotechnology and Biological Sciences Research Council (BB/M027252/2)
Biotechnology and Biological Sciences Research Council (BB/M027252/1)