AAV-mediated BMP7 gene therapy counteracts insulin resistance and obesity
Estefanía Casana, Verónica Jiménez, Claudia Jambrina, Victor Sacristan, Sergio Muñoz, Jordi Rodó, Ignasi Grass, Miquel García, Cristina Mallol, Xavier León, Alba Casellas, Víctor Sánchez, Sylvie Franckhauser, Tura Ferré, Sara Marcó, Fátima Bosch
Abstract
. 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.