Altered Lipid Moieties and Carbonyls in a Wistar Rat Dietary Model of Subclinical Fatty Liver: Potential Sex-Specific Biomarkers of Early Fatty Liver Disease?

Author:

Martín-Grau María12,Pardo-Tendero Mercedes12ORCID,Casanova Pilar12,Dromant Mar23,Marrachelli Vannina G.23,Morales Jose Manuel12ORCID,Borrás Consuelo23ORCID,Pisoni Serena3ORCID,Maestrini Sabrina4ORCID,Di Blasio Anna M.4,Monleon Daniel125ORCID

Affiliation:

1. Department of Pathology, University of Valencia, 46010 Valencia, Spain

2. University Clinical Hospital of Valencia Research Foundation (INCLIVA), 46010 Valencia, Spain

3. Department of Physiology, University of Valencia, 46010 Valencia, Spain

4. Laboratory of Molecular Genetics, Istituto Auxologico Italiano IRCCS, 20145 Milano, Italy

5. CIBERFES_ISCIII, 46010 Valencia, Spain

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a condition in which excess fat builds up in the liver. To date, there is a lack of knowledge about the subtype of lipid structures affected in the early stages of NAFLD. The aim of this study was to analyze serum and liver lipid moieties, specifically unsaturations and carbonyls, by nuclear magnetic resonance (NMR) in a subclinical Wistar rat model of NAFLD for detecting early alterations and potential sex dimorphisms. Twelve weeks of a high-fat diet (HFD) induced fat accumulation in the liver to a similar extent in male and female Wistar rats. In addition to total liver fat accumulation, Wistar rats showed a shift in lipid subtype composition. HFD rats displayed increased lipid carbonyls in both liver and serum, and decreased in unsaturated fatty acids (UFAs) and polyunsaturated fatty acids (PUFAs), with a much stronger effect in male than female animals. Our results revealed that the change in fat was not only quantitative but also qualitative, with dramatic shifts in relevant lipid structures. Finally, we compared the results found in Wistar rats with an analysis in a human patient cohort of extreme obesity. For the first time to our knowledge, lipid carbonyl levels and lipoproteins profiles were analyzed in the context of subclinical NAFLD. The association found between lipid carbonyls and alanine aminotransferase (ALT) in a human cohort of extremely obese individuals further supports the potential role of lipid moieties as biomarkers of early NAFLD.

Funder

University of Valencia

Ministry of Universities of Spain and the University of Valencia

Ministerio de Ciencia e Innovación of Spain

Instituto de Salud Carlos III (ISCIII) of Spain

Generalitat Valenciana of Spain

University of Valencia and the INCLIVA

EU Joint Programming Initiative Healthy Diet Healthy Life (HDHL) ISCIII

Italian Ministry of Health Project

Publisher

MDPI AG

Subject

Cell Biology,Clinical Biochemistry,Molecular Biology,Biochemistry,Physiology

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