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Adipocyte and Cell Biology

BMP7 overexpression in adipose tissue induces white adipogenesis and improves insulin sensitivity in ob/ob mice

International Journal of Obesity volume 45, pages 449–460 (2021)Cite this article

Subjects

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.

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Fig. 1: BMP7 increases fat mass and reduces white adipocyte size.
Fig. 2: BMP7 induces white adipogenesis and decreases WAT inflammation.
Fig. 3: WAT-derived BMP7 does neither induce brown adipogenesis nor enhance non-shivering thermogenesis.
Fig. 4: BMP7 ameliorates hepatic steatosis.
Fig. 5: BMP7 improves insulin sensitivity.
Fig. 6: Liver-derived BMP7 does not induce white adipogenesis.

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Acknowledgements

This work was supported by grants from Ministerio 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.

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Author notes

  1. These authors contributed equally: Estefania Casana, Veronica Jimenez

Authors and Affiliations

  1. Center of Animal Biotechnology and Gene Therapy (CBATEG), Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain

    Estefania Casana, Veronica Jimenez, Victor Sacristan, Sergio Muñoz, Claudia Jambrina, Jordi Rodó, Miquel Garcia, Cristina Mallol, Xavier León, Sylvie Franckhauser & Fatima Bosch

  2. Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain

    Estefania Casana, Veronica Jimenez, Victor Sacristan, Sergio Muñoz, Claudia Jambrina, Jordi Rodó, Miquel Garcia, Cristina Mallol, Xavier León, Sylvie Franckhauser & Fatima Bosch

  3. CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), 28029, Madrid, Spain

    Estefania Casana, Veronica Jimenez, Sergio Muñoz, Claudia Jambrina, Miquel Garcia, Xavier León, Sylvie Franckhauser & Fatima Bosch

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  1. Estefania Casana
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Contributions

EC, VJ, and FB designed and supervised experiments and analyzed data. EC, VJ, VS, SM, CJ, JR, MG, and CM generated reagents and performed experiments. XL produced AAV vectors. EC, VJ, SF, and FB contributed to discussion and wrote the manuscript.

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Correspondence to Fatima Bosch.

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Casana, E., Jimenez, V., Sacristan, V. et al. BMP7 overexpression in adipose tissue induces white adipogenesis and improves insulin sensitivity in ob/ob mice. Int J Obes 45, 449–460 (2021). https://doi.org/10.1038/s41366-020-00700-6

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