title: HMGA1 overexpression in adipose tissue impairs adipogenesis and prevents diet-induced obesity and insulin resistance.
abstract: High-Mobility-Group-A1 (HMGA1) proteins are non-histone proteins that regulate chromatin structure and gene expression during embryogenesis, tumourigenesis and immune responses. In vitro studies suggest that HMGA1 proteins may be required to regulate adipogenesis. To examine the role of HMGA1 in vivo, we generated transgenic mice overexpressing HMGA1 in adipose tissues. HMGA1 transgenic mice showed a marked reduction in white and brown adipose tissue mass that was associated with downregulation of genes involved in adipogenesis and concomitant upregulation of preadipocyte markers. Reduced adipogenesis and decreased fat mass were not associated with altered glucose homeostasis since HMGA1 transgenic mice fed a regular-chow diet exhibited normal glucose tolerance and insulin sensitivity. However, when fed a high-fat diet, overexpression of HMGA1 resulted in decreased body-weight gain, reduced fat mass, but improved insulin sensitivity and glucose tolerance. Although HMGA1 transgenic mice exhibited impaired glucose uptake in adipose tissue due to impaired adipogenesis, the increased glucose uptake observed in skeletal muscle may account for the improved glucose homeostasis. Our results indicate that HMGA1 plays an important function in the regulation of white and brown adipogenesis in vivo and suggests that impaired adipocyte differentiation and decreased fat mass is not always associated with impaired whole-body glucose homeostasis.
authors.affiliation: Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, Bellaterra, Spain.|Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: Altamira
authors.initials: A
authors.lastname: Arce-Cerezo
authors.affiliation: Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, Bellaterra, Spain.|Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Bellaterra, Spain.|Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain.
authors.forename: Miquel
authors.initials: M
authors.lastname: García
authors.affiliation: Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, Bellaterra, Spain.|Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: Aida
authors.initials: A
authors.lastname: Rodríguez-Nuevo
authors.affiliation: Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, Bellaterra, Spain.|Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Crosa-Bonell
authors.affiliation: Laboratory of Metabolism and Obesity, Vall d'Hebron-Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: Enguix
authors.affiliation: Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, Bellaterra, Spain.|Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Peró
authors.affiliation: Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, Bellaterra, Spain.|Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Bellaterra, Spain.|Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Muñoz
authors.affiliation: Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, Bellaterra, Spain.|Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Bellaterra, Spain.|Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain.
authors.forename: Carles
authors.initials: C
authors.lastname: Roca
authors.affiliation: Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, Bellaterra, Spain.|Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain.|Department of Anatomy and Animal Health, School of Veterinary Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Ramos
authors.affiliation: Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, Bellaterra, Spain.|Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Bellaterra, Spain.|Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Franckhauser
authors.affiliation: Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, Bellaterra, Spain.|Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Bellaterra, Spain.|Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain.
authors.forename: Ivet
authors.initials: I
authors.lastname: Elias
authors.affiliation: Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, Bellaterra, Spain.|Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Bellaterra, Spain.|Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain.
authors.forename: Tura
authors.initials: T
authors.lastname: Ferre
authors.affiliation: Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, Bellaterra, Spain.|Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Bellaterra, Spain.|Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Pujol
authors.affiliation: Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, Bellaterra, Spain.|Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain.|Department of Anatomy and Animal Health, School of Veterinary Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Ruberte
authors.affiliation: Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain.|Laboratory of Metabolism and Obesity, Vall d'Hebron-Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Josep A
authors.initials: JA
authors.lastname: Villena
authors.affiliation: Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, Bellaterra, Spain.|Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Bellaterra, Spain.|Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain.
authors.forename: Fàtima
authors.initials: F
authors.lastname: Bosch
authors.affiliation: Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, Bellaterra, Spain.|Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Bellaterra, Spain.|Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain.
authors.forename: Efrén
authors.initials: E
authors.lastname: Riu
mesh_terms: D050156:Adipogenesis / Q000235:genetics*; D000273:Adipose Tissue / Q000196:embryology / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000196:embryology / Q000378:metabolism; D050154:Adiposity / Q000235:genetics; D000818:Animals; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D024003:HMGA Proteins / Q000235:genetics*; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009765:Obesity / Q000209:etiology* / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics
chemical_list: D024003:HMGA Proteins; D005947:Glucose