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Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 and angiopoietin-like protein 4 are associated with the increase of lipoprotein lipase activity in epicardial adipose tissue from diabetic patients

  • Magalí Barchuk
    Affiliations
    Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Instituto de Fisiopatología y Bioquímica Clínica (INFIBIOC), Departamento de Bioquímica Clínica, Laboratorio de Lípidos y Aterosclerosis, Buenos Aires, Argentina
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  • Laura Schreier
    Affiliations
    Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Instituto de Fisiopatología y Bioquímica Clínica (INFIBIOC), Departamento de Bioquímica Clínica, Laboratorio de Lípidos y Aterosclerosis, Buenos Aires, Argentina
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  • Graciela López
    Affiliations
    Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Instituto de Fisiopatología y Bioquímica Clínica (INFIBIOC), Departamento de Bioquímica Clínica, Laboratorio de Lípidos y Aterosclerosis, Buenos Aires, Argentina
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  • Agata Cevey
    Affiliations
    Universidad de Buenos Aires, CONICET, Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Facultad de Medicina, Buenos Aires, Argentina
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  • Julio Baldi
    Affiliations
    Universidad de Buenos Aires, Hospital de Clínicas “José de San Martín”, División de Cirugía Cardíaca, Buenos Aires, Argentina
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  • María del Carmen Fernandez Tomé
    Affiliations
    Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Biología Celular y Molecular, Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), CONICET, Buenos Aires, Argentina
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  • Nora Goren
    Affiliations
    Universidad de Buenos Aires, CONICET, Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Facultad de Medicina, Buenos Aires, Argentina
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  • Miguel Rubio
    Affiliations
    Universidad de Buenos Aires, Hospital de Clínicas “José de San Martín”, División de Cirugía Cardíaca, Buenos Aires, Argentina
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  • Verónica Miksztowicz
    Affiliations
    Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Instituto de Fisiopatología y Bioquímica Clínica (INFIBIOC), Departamento de Bioquímica Clínica, Laboratorio de Lípidos y Aterosclerosis, Buenos Aires, Argentina

    Universidad de Buenos Aires, CONICET, Facultad de Farmacia y Bioquímica, Buenos Aires, Argentina
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  • Gabriela Berg
    Correspondence
    Corresponding author. Junín 956, CABA, Argentina.
    Affiliations
    Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Instituto de Fisiopatología y Bioquímica Clínica (INFIBIOC), Departamento de Bioquímica Clínica, Laboratorio de Lípidos y Aterosclerosis, Buenos Aires, Argentina

    Universidad de Buenos Aires, CONICET, Facultad de Farmacia y Bioquímica, Buenos Aires, Argentina
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      Highlights

      • LPL activity was increased in EAT from DM2 patients.
      • In DM2, increased GPIHBP1 and decreased ANGPTL4 EAT expression modulated LPL activity.
      • Higher EAT LPL activity was responsible for TG-VLDL catabolism and fatty acids release.
      • EAT VLDL receptor was inversely associated with circulating VLDL mass and TG-VLDL.
      • The higher EAT LPL activity in DM2 could be responsible for the increased EAT volume.

      Abstract

      Background and aims

      Epicardial adipose tissue (EAT) is a visceral AT, surrounding myocardium and coronary arteries. Its volume is higher in Type 2 diabetic (DM2) patients, associated with cardiovascular disease risk. Lipoprotein lipase (LPL) hydrolyses triglycerides (TG) from circulating lipoproteins, supplying fatty acids to AT, contributing to its expansion. We aimed to evaluate LPL expression and activity in EAT from DM2 and no DM2 patients, and its regulators ANGPTL4, GPIHBP1 and PPARγ levels, together with VLDLR expression and EAT LPL association with VLDL characteristics.

      Methods

      We studied patients undergoing coronary by-pass graft (CABG) divided into CABG-DM2 (n = 21) and CABG-noDM2 (n = 29), and patients without CABG (No CABG, n = 30). During surgery, EAT and subcutaneous AT (SAT) were obtained, in which LPL activity, gene and protein expression, its regulators and VLDLR protein levels were determined. Isolated circulating VLDLs were characterized.

      Results

      EAT LPL activity was higher in CABG-DM2 compared to CABG-noDM2 and No CABG (p=0.002 and p<0.001) and in CABG-noDM2 compared to No CABG (p=0.02), without differences in its expression. ANGPTL4 levels were higher in EAT from No CABG compared to CABG-DM2 and CABG-noDM2 (p<0.001). GPIHBP1 levels were higher in EAT from CABG-DM2 and CABG-noDM2 compared to No CABG (p= 0.04). EAT from CABG-DM2 presented higher PPARγ levels than CABG-noDM2 and No CABG (p=0.02 and p=0.03). No differences were observed in VLDL composition between groups, although EAT LPL activity was inversely associated with VLDL-TG and TG/protein index (p<0.05).

      Conclusions

      EAT LPL regulation would be mainly post-translational. The higher LPL activity in DM2 could be partly responsible for the increase in EAT volume.

      Graphical abstract

      Keywords

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