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Angiopoietin-like protein 8 (ANGPTL8) in pregnancy: a brown adipose tissue–derived endocrine factor with a potential role in fetal growth

  • Bruno Martinez-Perez
    Affiliations
    Hospital Universitari de Tarragona Joan XXIII, Institut Investigació Sanitaria Pere Virgili, Universitat Rovira i Virgili, Tarragona, Spain
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  • Miriam Ejarque
    Affiliations
    Hospital Universitari de Tarragona Joan XXIII, Institut Investigació Sanitaria Pere Virgili, Universitat Rovira i Virgili, Tarragona, Spain

    CIBER Diabetes y Enfermedades Metabólicas Asociadas (CIBERdem), Instituto de Salud Carlos III, Madrid, Spain
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  • Cristina Gutierrez
    Affiliations
    Hospital Universitari de Tarragona Joan XXIII, Institut Investigació Sanitaria Pere Virgili, Universitat Rovira i Virgili, Tarragona, Spain

    CIBER Diabetes y Enfermedades Metabólicas Asociadas (CIBERdem), Instituto de Salud Carlos III, Madrid, Spain
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  • Catalina Nuñez-Roa
    Affiliations
    Hospital Universitari de Tarragona Joan XXIII, Institut Investigació Sanitaria Pere Virgili, Universitat Rovira i Virgili, Tarragona, Spain

    CIBER Diabetes y Enfermedades Metabólicas Asociadas (CIBERdem), Instituto de Salud Carlos III, Madrid, Spain
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  • Kelly Roche
    Affiliations
    Hospital Universitari de Tarragona Joan XXIII, Institut Investigació Sanitaria Pere Virgili, Universitat Rovira i Virgili, Tarragona, Spain

    CIBER Diabetes y Enfermedades Metabólicas Asociadas (CIBERdem), Instituto de Salud Carlos III, Madrid, Spain
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  • Rocio Vila-Bedmar
    Affiliations
    Departamento de Biología Molecular and Centro de Biología Molecular Severo Ochoa (UAM-CSIC), Madrid, Spain

    Instituto de Investigación Sanitaria La Princesa, Madrid, Spain
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  • Mónica Ballesteros
    Affiliations
    Hospital Universitari de Tarragona Joan XXIII, Institut Investigació Sanitaria Pere Virgili, Universitat Rovira i Virgili, Tarragona, Spain
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  • Ibon Redondo-Angulo
    Affiliations
    Departament de Bioquimica i Biologia Molecular, Institut de Biomedicina, Universitat de Barcelona, Barcelona, Spain

    CIBER Fisiopatologia de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain
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  • Anna Planavila
    Affiliations
    Departament de Bioquimica i Biologia Molecular, Institut de Biomedicina, Universitat de Barcelona, Barcelona, Spain

    CIBER Fisiopatologia de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain
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  • Francesc Villarroya
    Affiliations
    Departament de Bioquimica i Biologia Molecular, Institut de Biomedicina, Universitat de Barcelona, Barcelona, Spain

    CIBER Fisiopatologia de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain
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  • Joan Vendrell
    Affiliations
    Hospital Universitari de Tarragona Joan XXIII, Institut Investigació Sanitaria Pere Virgili, Universitat Rovira i Virgili, Tarragona, Spain

    CIBER Diabetes y Enfermedades Metabólicas Asociadas (CIBERdem), Instituto de Salud Carlos III, Madrid, Spain
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  • Sonia Fernández-Veledo
    Correspondence
    Reprint requests: Sonia Fernández-Veledo and Ana Megía, Research Unit Hospital Universitari de Tarragona Joan XXIII, C/ Dr. Mallafré Guasch, 4, 43007 Tarragona, Spain
    Affiliations
    Hospital Universitari de Tarragona Joan XXIII, Institut Investigació Sanitaria Pere Virgili, Universitat Rovira i Virgili, Tarragona, Spain

    CIBER Diabetes y Enfermedades Metabólicas Asociadas (CIBERdem), Instituto de Salud Carlos III, Madrid, Spain
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  • Ana Megía
    Correspondence
    Reprint requests: Sonia Fernández-Veledo and Ana Megía, Research Unit Hospital Universitari de Tarragona Joan XXIII, C/ Dr. Mallafré Guasch, 4, 43007 Tarragona, Spain
    Affiliations
    Hospital Universitari de Tarragona Joan XXIII, Institut Investigació Sanitaria Pere Virgili, Universitat Rovira i Virgili, Tarragona, Spain

    CIBER Diabetes y Enfermedades Metabólicas Asociadas (CIBERdem), Instituto de Salud Carlos III, Madrid, Spain
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      Angiopoietin-like protein 8 (ANGPTL8), a protein implicated in lipid and glucose homeostasis, is present only in mammals, suggesting that it is involved in processes unique to these vertebrates such as pregnancy and homeothermy. We explored the role of ANGPTL8 in maternal-fetal crosstalk and its relationship with newborn adiposity. In a longitudinal analysis of healthy pregnant women, ANGPTL8 levels decreased progressively during pregnancy although remained higher than levels in the postpartum period. In a cross-sectional observational study of women with or without gestational diabetes mellitus (GDM), and their offspring, ANGPTL8 levels were higher in venous cord blood than those in maternal blood and were significantly lower in GDM patients than those in healthy women. Infants small for gestational age and with low-fat mass had the highest ANGPTL8 cord blood levels. Studies in vitro revealed that ANGPTL8 was secreted by brown adipocytes and its expression was increased in experimental models of white-to-brown fat conversion. In addition, ANGPTL8 induced the expression of markers of brown adipocytes. The high levels of ANGPTL8 found in fetal life together with its relationship with newborn adiposity and brown adipose tissue point to ANGPTL8 as a potential new player in the modulation of the thermogenic machinery during the fetal-neonatal transition.

      Abbreviations:

      ANGPTL8 (angiopoietin-like protein 8), GDM (gestational diabetes mellitus), WAT (white adipose tissue), BAT (brown adipose tissue), OGTT (oral glucose tolerance test), BMI (body mass index), LGA (large for gestational age), AGA (adequate for gestational age), SGA (small for gestational age), SSF (sum of 3 skinfolds), HOMA-IR (insulin resistance homeostatic model assessment), HOMA-B (beta cell function—homeostatic model assessment), hWA (human white adipocytes), hBA (human brown adipocytes), mBA (murine brown adipocytes), hASCS (adipose-derived stem cells), UCP1 (uncoupling protein 1)
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