BMP7 overexpression in adipose tissue induces white adipogenesis and improves insulin sensitivity in ob/ob mice
Casaña Lorente, Estefania (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Jimenez, Veronica (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Sacristan, Victor (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Muñoz, Sergio (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Jambrina Pallarés, Claudia (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Rodó Morera, Jordi (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Garcia, Miquel (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Mallol, Cristina (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
León, Xavier (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Franckhauser, Sylvie (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Bosch i Tubert, Fàtima (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Date:	2021
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.
Grants:	Ministerio de Economía y Competitividad SAF2014-54866R Ministerio de Economía y Competitividad SAF2017-86266R Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-1669 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-1508
Note:	Altres ajuts: ICREA Academia Award
Rights:	Tots els drets reservats.
Language:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Subject:	Endocrinology, diabetes and metabolism ; Nutrition and dietetics ; SDG 3 - Good health and well-being
Published in:	International Journal of Obesity, Vol. 45, Issue 2 (February 2021) , p. 449-460, ISSN 1476-5497

DOI: 10.1038/s41366-020-00700-6
PMID: 33110143

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