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

• Published in: International Journal of Obesity 2021-02, Vol.45 (2), p.449-460
• Main Authors: Casana, Estefania, Jimenez, Veronica, Sacristan, Victor, Muñoz, Sergio, Jambrina, Claudia, Rodó, Jordi, Garcia, Miquel, Mallol, Cristina, León, Xavier, Franckhauser, Sylvie, Bosch, Fatima
• Format: Article
• Language: English
• Subjects: 13/51; 14/63; 38/1; 38/77; 42/44; 631/1647/767/1424; 631/443/319/1642/393; 64/60; Adipocytes; Adipogenesis; Adipogenesis - genetics; Adipose tissue; Adipose Tissue, White - metabolism; Adipose tissues; Animal models; Animals; Autocrine signalling; Body fat; Bone morphogenetic protein 7; Bone Morphogenetic Protein 7 - genetics; Bone Morphogenetic Protein 7 - metabolism; Bone morphogenetic proteins; Cell development (Biology); Development and progression; Enlargement; Epidemiology; Eutrophication; Expression vectors; Fatty liver; Gene expression; Genetic engineering; Health aspects; Health Promotion and Disease Prevention; Hormones; Hyperplasia; Insulin; Insulin resistance; Insulin Resistance - genetics; Internal Medicine; Lipids; Liver; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolites; Mice; Mice, Obese; Obesity; Obesity - genetics; Obesity - metabolism; Paracrine signalling; Physiological aspects; Public Health; Sensitivity; Steatosis
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/s41366-020-00700-6

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.