Hepatic Lipidomics and Molecular Imaging in a Murine Non-Alcoholic Fatty Liver Disease Model: Insights into Molecular Mechanisms

• Published in: Biomolecules (Basel, Switzerland) Vol. 10; no. 9; p. 1275
• Main Authors: Rodríguez-Calvo, Ricardo, Samino, Sara, Girona, Josefa, Martínez-Micaelo, Neus, Ràfols, Pere, García-Altares, María, Guaita-Esteruelas, Sandra, Junza, Alexandra, Heras, Mercedes, Yanes, Oscar, Correig, Xavier, Masana, Lluis
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 03-09-2020; MDPI
• Subjects: adipokines; Adiponectin; Adipose tissue; Animal models; Biomarkers; Cholesterol; Chromatography; Dehydrogenases; FABP4; Fatty acids; Fatty liver; Gene expression; High fat diet; Inflammation; Laboratory animals; Leptin; Lipid metabolism; lipidome; Lipids; Lipogenesis; Lipoproteins; Liquid chromatography; Liver diseases; liver triglycerides; Mass spectroscopy; Metabolism; Molecular modelling; NAFLD; Obesity; Oxidation; Plasma; Polymerase chain reaction; Triglycerides; Tumor necrosis factor-TNF; United States > US; Spain; NAFLD; adipokines; FABP4; lipidome; inflammation; liver triglycerides
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom10091275

An imbalance between hepatic fatty acid uptake and removal results in ectopic fat accumulation, which leads to non-alcoholic fatty liver disease (NAFLD). The amount and type of accumulated triglycerides seem to play roles in NAFLD progression; however, a complete understanding of how triglycerides contribute to NAFLD evolution is lacking. Our aim was to evaluate triglyceride accumulation in NAFLD in a murine model and its associations with molecular mechanisms involved in liver damage and adipose tissue-liver cross talk by employing lipidomic and molecular imaging techniques. C57BL/6J mice fed a high-fat diet (HFD) for 12 weeks were used as a NAFLD model. Standard-diet (STD)-fed animals were used as controls. Standard liver pathology was assessed using conventional techniques. The liver lipidome was analyzed by liquid chromatography-mass spectrometry (LC-MS) and laser desorption/ionization-mass spectrometry (LDI-MS) tissue imaging. Liver triglycerides were identified by MS/MS. The transcriptome of genes involved in intracellular lipid metabolism and inflammation was assessed by RT-PCR. Plasma leptin, resistin, adiponectin, and FABP4 levels were determined using commercial kits. HFD-fed mice displayed increased liver lipid content. LC-MS analyses identified 14 triglyceride types that were upregulated in livers from HFD-fed animals. Among these 14 types, 10 were identified in liver cross sections by LDI-MS tissue imaging. The accumulation of these triglycerides was associated with the upregulation of lipogenesis and inflammatory genes and the downregulation of β-oxidation genes. Interestingly, the levels of plasma FABP4, but not of other adipokines, were positively associated with 8 of these triglycerides in HFD-fed mice but not in STD-fed mice. Our findings suggest a putative role of FABP4 in the liver-adipose tissue cross talk in NAFLD.