AAV-mediated BMP7 gene therapy counteracts insulin resistance and obesity

Estefania Casana, Veronica Jimenez, Claudia Jambrina, Victor Sacristan, Sergio Muñoz, Jordi Rodo, Ignasi Grass, Miquel Garcia, Cristina Mallol, Xavier León, Alba Casellas, Víctor Sánchez, Sylvie Franckhauser, Tura Ferré, Sara Marcó, Fatima Bosch*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)


Type 2 diabetes, insulin resistance, and obesity are strongly associated and are a major health problem worldwide. Obesity largely results from a sustained imbalance between energy intake and expenditure. Therapeutic approaches targeting metabolic rate may counteract body weight gain and insulin resistance. Bone morphogenic protein 7 (BMP7) has proven to enhance energy expenditure by inducing non-shivering thermogenesis in short-term studies in mice treated with the recombinant protein or adenoviral vectors encoding BMP7. To achieve long-term BMP7 effects, the use of adeno-associated viral (AAV) vectors would provide sustained production of the protein after a single administration. Here, we demonstrated that treatment of high-fat-diet-fed mice and ob/ob mice with liver-directed AAV-BMP7 vectors enabled a long-lasting increase in circulating levels of this factor. This rise in BMP7 concentration induced browning of white adipose tissue (WAT) and activation of brown adipose tissue, which enhanced energy expenditure, and reversed WAT hypertrophy, hepatic steatosis, and WAT and liver inflammation, ultimately resulting in normalization of body weight and insulin resistance. This study highlights the potential of AAV-BMP7-mediated gene therapy for the treatment of insulin resistance, type 2 diabetes, and obesity.

Original languageEnglish
Pages (from-to)190-204
Number of pages15
JournalMolecular Therapy - Methods and Clinical Development
Publication statusPublished - 9 Jun 2022


  • AAV
  • BMP7
  • gene therapy
  • insulin resistance
  • obesity
  • type 2 diabetes


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