title: Angiopoietin-like protein 8 (ANGPTL8) in pregnancy: a brown adipose tissue-derived endocrine factor with a potential role in fetal growth.
abstract: 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.
authors.affiliation: Hospital Universitari de Tarragona Joan XXIII, Institut Investigació Sanitaria Pere Virgili, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: Bruno
authors.initials: B
authors.lastname: Martinez-Perez
authors.affiliation: 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.
authors.forename: Miriam
authors.initials: M
authors.lastname: Ejarque
authors.affiliation: 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.
authors.forename: Cristina
authors.initials: C
authors.lastname: Gutierrez
authors.affiliation: 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.
authors.forename: Catalina
authors.initials: C
authors.lastname: Nuñez-Roa
authors.affiliation: 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.
authors.forename: Kelly
authors.initials: K
authors.lastname: Roche
authors.affiliation: Departamento de Biología Molecular and Centro de Biología Molecular Severo Ochoa (UAM-CSIC), Madrid, Spain; Instituto de Investigación Sanitaria La Princesa, Madrid, Spain.
authors.forename: Rocio
authors.initials: R
authors.lastname: Vila-Bedmar
authors.affiliation: Hospital Universitari de Tarragona Joan XXIII, Institut Investigació Sanitaria Pere Virgili, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Ballesteros
authors.affiliation: 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.
authors.forename: Ibon
authors.initials: I
authors.lastname: Redondo-Angulo
authors.affiliation: 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.
authors.forename: Anna
authors.initials: A
authors.lastname: Planavila
authors.affiliation: 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.
authors.forename: Francesc
authors.initials: F
authors.lastname: Villarroya
authors.affiliation: 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.
authors.forename: Joan
authors.initials: J
authors.lastname: Vendrell
authors.affiliation: 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. Electronic address: sonia.fernandezveledo@gmail.com.
authors.forename: Sonia
authors.initials: S
authors.lastname: Fernández-Veledo
authors.affiliation: 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. Electronic address: ana.megia@gmail.com.
authors.forename: Ana
authors.initials: A
authors.lastname: Megía
mesh_terms: D052437:Adipocytes, Brown / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000328:Adult; D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000097:blood*; D000818:Animals; D004703:Endocrine System / Q000378:metabolism*; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D047109:Fetal Development; D006801:Humans; D008810:Mice, Inbred C57BL; D036361:Peptide Hormones / Q000097:blood*; D010641:Phenotype; D049590:Postpartum Period / Q000378:metabolism; D011247:Pregnancy
chemical_list: C576683:ANGPTL8 protein, human; C000595899:ANGPTL8 protein, mouse; D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D036361:Peptide Hormones