Articles producció científica> Medicina i Cirurgia

Regulatory effects of arachidonate 5-lipoxygenase on hepatic microsomal TG transfer protein activity and VLDL-triglyceride and apoB secretion in obese mice

  • Identification data

    Identifier: imarina:625819
    Handle: http://hdl.handle.net/20.500.11797/imarina625819
  • Authors:

    Lopez-Parra, Marta
    Titos, Esther
    Horrillo, Raquel
    Gonzalez-Periz, Ana
    Martinez-Clemente, Marcos
    Planaguma, Anna
    Masferrer, Jaime
    Arroyo, Vicente
    Claria, Joan
  • Others:

    Author, as appears in the article.: Lopez-Parra, Marta; Titos, Esther; Horrillo, Raquel; Gonzalez-Periz, Ana; Martinez-Clemente, Marcos; Planaguma, Anna; Masferrer, Jaime; Arroyo, Vicente; Claria, Joan
    Department: Medicina i Cirurgia
    URV's Author/s: Ferre Pallas, Natalia
    Keywords: Vldl-tg Thrombosis Hepatic steatosis Expression Arachidonate 5-lo Activation Acid
    Abstract: As 5-lipoxygenase (5-LO) is an emerging target in obesity and insulin resistance, we have investigated whether this arachidonate pathway is also implicated in the progression of obesity-related fatty liver disease. Our results show that 5-LO activity and 5-LO-derived product levels are significantly elevated in the liver of obese ob/ob mice with respect to wild-type controls. Treatment of ob/ob mice with a selective 5-LO inhibitor exerted a remarkable protection from hepatic steatosis as revealed by decreased oil red-O staining and reduced hepatic triglyceride (TG) concentrations. In addition, 5-LO inhibition in ob/ob mice downregulated genes involved in hepatic fatty acid uptake (i.e., L-FABP and FAT/CD36) and normalized peroxisome proliferator-activated receptor alpha (PPARalpha) and acyl-CoA oxidase expression, whereas the expression of lipogenic genes [i.e., fatty acid synthase (FASN) and SREBP-1c] remained unaltered. Furthermore, 5-LO inhibition restored hepatic microsomal TG transfer protein (MTP) activity in parallel with a stimulation of hepatic VLDL-TG and apoB secretion in ob/ob mice. Consistent with these findings, 5-LO products directly inhibited MTP activity and triggered cytosolic TG accumulation in CC-1 cells, a murine hepatocyte cell line. Taken together, these findings identify a novel steatogenic role for 5-LO in the liver through mechanisms involving the regulation of hepatic MTP activity and VLDL-TG and apoB secretion.
    Thematic Areas: Zootecnia / recursos pesqueiros Química Medicina veterinaria Medicina iii Medicina ii Medicina i Farmacia Endocrinology Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Cell biology Biodiversidade Biochemistry & molecular biology Biochemistry
    licence for use: https://creativecommons.org/licenses/by/3.0/es/
    ISSN: 00222275
    Author's mail: natalia.ferre@urv.cat
    Author identifier: 0000-0002-2838-1525
    Record's date: 2023-02-18
    Papper version: info:eu-repo/semantics/publishedVersion
    Link to the original source: https://www.jlr.org/article/S0022-2275(20)34583-1/fulltext
    Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/
    Papper original source: Journal Of Lipid Research. 49 (12): 2513-2523
    APA: Lopez-Parra, Marta; Titos, Esther; Horrillo, Raquel; Gonzalez-Periz, Ana; Martinez-Clemente, Marcos; Planaguma, Anna; Masferrer, Jaime; Arroyo, Vicent (2008). Regulatory effects of arachidonate 5-lipoxygenase on hepatic microsomal TG transfer protein activity and VLDL-triglyceride and apoB secretion in obese mice. Journal Of Lipid Research, 49(12), 2513-2523. DOI: 10.1194/jlr.M800101-JLR200
    Article's DOI: 10.1194/jlr.M800101-JLR200
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2008
    Publication Type: Journal Publications
  • Keywords:

    Biochemistry,Biochemistry & Molecular Biology,Cell Biology,Endocrinology
    Vldl-tg
    Thrombosis
    Hepatic steatosis
    Expression
    Arachidonate 5-lo
    Activation
    Acid
    Zootecnia / recursos pesqueiros
    Química
    Medicina veterinaria
    Medicina iii
    Medicina ii
    Medicina i
    Farmacia
    Endocrinology
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
    Cell biology
    Biodiversidade
    Biochemistry & molecular biology
    Biochemistry
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