Estefania Casana1,2,3, Veronica Jimenez1,2,3, Victor Sacristan1,2, Sergio Muñoz1,2,3, Claudia Jambrina1,2,3, Jordi Rodó1,2, Miquel Garcia1,2,3, Cristina Mallol1,2, Xavier León1,2,3, Sylvie Franckhauser1,2,3, Fatima Bosch4,5,6. 1. Center of Animal Biotechnology and Gene Therapy (CBATEG), Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain. 2. Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain. 3. CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), 28029, Madrid, Spain. 4. Center of Animal Biotechnology and Gene Therapy (CBATEG), Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain. fatima.bosch@uab.cat. 5. Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain. fatima.bosch@uab.cat. 6. CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), 28029, Madrid, Spain. fatima.bosch@uab.cat.
Abstract
BACKGROUND/ OBJECTIVES: During obesity, hypertrophic enlargement of white adipose tissue (WAT) promotes ectopic lipid deposition and development of insulin resistance. In contrast, WAT hyperplasia is associated with preservation of insulin sensitivity. The complex network of factors that regulates white adipogenesis is not fully understood. Bone morphogenic protein 7 (BMP7) can induce brown adipogenesis, but its role on white adipogenesis remains to be elucidated. Here, we assessed BMP7-mediated effects on white adipogenesis in ob/ob mice. METHODS: BMP7 was overexpressed in either WAT or liver of ob/ob mice using adeno-associated viral (AAV) vectors. Analysis of gene expression, histological and morphometric alterations, and metabolites and hormones concentrations were carried out. RESULTS: Overexpression of BMP7 in adipocytes of subcutaneous and visceral WAT increased fat mass, the proportion of small-size adipocytes and the expression of adipogenic and mature adipocyte genes, suggesting induction of adipogenesis irrespective of fat depot. These changes were associated with reduced hepatic steatosis and improved insulin sensitivity. In contrast, liver-specific overproduction of BMP7 did not promote WAT hyperplasia despite BMP7 circulating levels were similar to those achieved after genetic engineering of WAT. CONCLUSIONS: This study unravels a new autocrine/paracrine role of BMP7 on white adipogenesis and highlights that BMP7 may modulate WAT plasticity and increase insulin sensitivity.
BACKGROUND/ OBJECTIVES: During obesity, hypertrophic enlargement of white adipose tissue (WAT) promotes ectopic lipid deposition and development of insulin resistance. In contrast, WAT hyperplasia is associated with preservation of insulin sensitivity. The complex network of factors that regulates white adipogenesis is not fully understood. Bone morphogenic protein 7 (BMP7) can induce brown adipogenesis, but its role on white adipogenesis remains to be elucidated. Here, we assessed BMP7-mediated effects on white adipogenesis in ob/ob mice. METHODS: BMP7 was overexpressed in either WAT or liver of ob/ob mice using adeno-associated viral (AAV) vectors. Analysis of gene expression, histological and morphometric alterations, and metabolites and hormones concentrations were carried out. RESULTS: Overexpression of BMP7 in adipocytes of subcutaneous and visceral WAT increased fat mass, the proportion of small-size adipocytes and the expression of adipogenic and mature adipocyte genes, suggesting induction of adipogenesis irrespective of fat depot. These changes were associated with reduced hepatic steatosis and improved insulin sensitivity. In contrast, liver-specific overproduction of BMP7 did not promote WAT hyperplasia despite BMP7 circulating levels were similar to those achieved after genetic engineering of WAT. CONCLUSIONS: This study unravels a new autocrine/paracrine role of BMP7 on white adipogenesis and highlights that BMP7 may modulate WAT plasticity and increase insulin sensitivity.
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