TY - JOUR
T1 - BMP7 overexpression in adipose tissue induces white adipogenesis and improves insulin sensitivity in ob/ob mice
AU - Casana, Estefania
AU - Jimenez, Veronica
AU - Sacristan, Victor
AU - Muñoz, Sergio
AU - Jambrina, Claudia
AU - Rodó, Jordi
AU - Garcia, Miquel
AU - Mallol, Cristina
AU - León, Xavier
AU - Franckhauser, Sylvie
AU - Bosch, Fatima
N1 - Funding Information:
Acknowledgements This work was supported by grants from Minis-terio de Economía y Competitividad (MINECO) and FEDER, Plan Nacional I+D+I (SAF2014-54866R and SAF2017-86266R), and Generalitat de Catalunya (2014 SGR 1669, 2017 SGR 1508, ICREA Academia Award to F.B.), Spain, and the European Foundation for the Study of Diabetes (EFSD/MSD European Research Programme on Novel Therapies for Type 2 Diabetes, 2013). VJ was recipient of a post-doctoral research fellowship from EFSD/Lilly. EC, VS, and CM received a predoctoral fellowship from Ministerio de Educación, Cultura y Deporte, JR from Ministerio de Economía y Competitividad, Spain. The authors thank Marta Moya, Sara Darriba, Tura Ferré, Maria Molas, Jennifer Barrero, and Lídia Hernández for technical assistance.
Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2020/10/27
Y1 - 2020/10/27
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85094175365&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/64f4f727-594c-3273-a6a3-05e60aa7ea6c/
U2 - 10.1038/s41366-020-00700-6
DO - 10.1038/s41366-020-00700-6
M3 - Article
C2 - 33110143
AN - SCOPUS:85094175365
SN - 0307-0565
VL - 45
SP - 449
EP - 460
JO - International Journal of Obesity
JF - International Journal of Obesity
IS - 2
ER -