Articles producció científica> Medicina i Cirurgia

Hepatic lipidomics and molecular imaging in a murine non-alcoholic fatty liver disease model: Insights into molecular mechanisms

  • Identification data

    Identifier: imarina:8505184
    Authors:
    Rodriguez-Calvo, RicardoSamino, SaraGirona, JosefaMartinez-Micaelo, NeusRafols, PereGarcia-Altares, MariaGuaita-Esteruelas, SandraJunza, AlexandraHeras, MercedesYanes, OscarCorreig, XavierMasana, Lluis
    Abstract:
    © 2020 by the authors. Licensee MDPI, Basel, Switzerland. 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-fe
  • Others:

    Author, as appears in the article.: Rodriguez-Calvo, Ricardo; Samino, Sara; Girona, Josefa; Martinez-Micaelo, Neus; Rafols, Pere; Garcia-Altares, Maria; Guaita-Esteruelas, Sandra; Junza, Alexandra; Heras, Mercedes; Yanes, Oscar; Correig, Xavier; Masana, Lluis
    Department: Enginyeria Electrònica, Elèctrica i Automàtica Medicina i Cirurgia
    URV's Author/s: Correig Blanchar, Francesc Xavier / Garcia-Altares Pérez, Maria / Girona Tell, Josefa / GUAITA ESTERUELAS, SANDRA / HERAS IBAÑEZ, MERCEDES / Junza Martínez, Alexandra / Martínez Micaelo, Nieves Beatriz / Masana Marín, Luis / Ràfols Soler, Pere / Rodríguez Calvo, Ricardo / SAMINO GENÉ, SARA / Yanes Torrado, Óscar
    Keywords: Triglycerides Tandem mass spectrometry Stress Steatosis Steatohepatitis Spectrometry, mass, matrix-assisted laser desorption-ionization Resistin Pathogenesis Non-alcoholic fatty liver disease Nafld Molecular imaging Mice, inbred c57bl Male Liver triglycerides Liver Lipidomics Lipidome Lipid metabolism Leptin Insulin-resistance Inhibition Inflammation Fatty acids Fatty acid-binding proteins Fabp4 protein, mouse Fabp4 Endoplasmic-reticulum Disease models, animal Diet, high-fat De-novo lipogenesis Chromatography, liquid Animals Alpha Adipose tissue Adiponectin Adipokines Acid-binding protein nafld lipidome inflammation fabp4 adipokines
    Abstract: © 2020 by the authors. Licensee MDPI, Basel, Switzerland. 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.
    Thematic Areas: Química Molecular biology Materiais General medicine Farmacia Ensino Biochemistry & molecular biology Biochemistry
    licence for use: https://creativecommons.org/licenses/by/3.0/es/
    ISSN: 2218273X
    Author's mail: josefa.girona@urv.cat ricardo.rodriguez@urv.cat oscar.yanes@urv.cat neus.martinez@urv.cat alexandra.junza@urv.cat maria.garcia-altares@urv.cat pere.rafols@urv.cat josefa.girona@urv.cat xavier.correig@urv.cat luis.masana@urv.cat
    Author identifier: 0000-0002-6267-8779 0000-0003-3695-7157 0000-0001-7205-0419 0000-0002-9240-4058 0000-0002-6267-8779 0000-0002-6902-3054 0000-0002-0789-4954
    Record's date: 2024-10-12
    Papper version: info:eu-repo/semantics/publishedVersion
    Link to the original source: https://www.mdpi.com/2218-273X/10/9/1275
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Papper original source: Biomolecules. 10 (9): 1-15
    APA: Rodriguez-Calvo, Ricardo; Samino, Sara; Girona, Josefa; Martinez-Micaelo, Neus; Rafols, Pere; Garcia-Altares, Maria; Guaita-Esteruelas, Sandra; Junza, (2020). Hepatic lipidomics and molecular imaging in a murine non-alcoholic fatty liver disease model: Insights into molecular mechanisms. Biomolecules, 10(9), 1-15. DOI: 10.3390/biom10091275
    Article's DOI: 10.3390/biom10091275
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2020
    Publication Type: Journal Publications
  • Keywords:

    Biochemistry,Biochemistry & Molecular Biology,Molecular Biology
    Triglycerides
    Tandem mass spectrometry
    Stress
    Steatosis
    Steatohepatitis
    Spectrometry, mass, matrix-assisted laser desorption-ionization
    Resistin
    Pathogenesis
    Non-alcoholic fatty liver disease
    Nafld
    Molecular imaging
    Mice, inbred c57bl
    Male
    Liver triglycerides
    Liver
    Lipidomics
    Lipidome
    Lipid metabolism
    Leptin
    Insulin-resistance
    Inhibition
    Inflammation
    Fatty acids
    Fatty acid-binding proteins
    Fabp4 protein, mouse
    Fabp4
    Endoplasmic-reticulum
    Disease models, animal
    Diet, high-fat
    De-novo lipogenesis
    Chromatography, liquid
    Animals
    Alpha
    Adipose tissue
    Adiponectin
    Adipokines
    Acid-binding protein
    nafld
    lipidome
    inflammation
    fabp4
    adipokines
    Química
    Molecular biology
    Materiais
    General medicine
    Farmacia
    Ensino
    Biochemistry & molecular biology
    Biochemistry
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