Bone morphogenetic protein-3b (BMP-3b) is a member of the transforming growth factor-β superfamily and has several activities that differ from those of other BMPs. We previously found that BMP-3b is highly expressed in adipocytes, its level is increased during obesity, and it inhibits adipogenesis by suppressing peroxisome proliferator-activated receptor γ (PPARγ) in vitro. However, the function of BMP-3b in adipose tissues in vivo remains unknown.
To determine the role of BMP-3b overexpression in adipose tissues in vivo, we generated transgenic mice (BMP-3b Tg) by using a conditional overexpression approach in fatty acid-binding protein 4-expressing adipocytes. We examined BMP-3b Tg mice fed a high-fat diet to elucidate the effects of BMP-3b on obesity. Adipocyte function was evaluated as expression of adipogenic and lipogenic markers in adipose tissue. We also performed glucose and insulin tolerance tests (GTT and ITT, respectively), and biochemical analysis of serum and measured energy expenditure by indirect calorimetry.
BMP-3b Tg mice fed a high-fat diet showed decreases in weight gain, fat-pad mass and adipocyte area, compared with wild-type mice. The adipose tissues of BMP-3b Tg mice showed downregulated expression of PPARγ and its target gene encoding fatty acid translocase/CD36. In addition, BMP-3b Tg mice had decreased blood glucose levels on GTT and ITT, and their serum leptin levels were decreased and adiponectin concentrations were increased. These changes in BMP-3b Tg mice were accompanied by increased energy expenditure, indicated as increased locomotor activity and oxygen consumption.
These results provide in vivo evidence that BMP-3b regulates adipocyte function to cause an anti-obesity effect.
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We thank Dr J Miyazaki for providing the pCAG-CAT-EGFP plasmid, Dr M Yoshimoto for guidance and helpful advice on indirect calorimetry, and Dr K Miura for helpful advice on western blotting. We appreciate the excellent technical assistance of Ms M Miyazaki, Ms Y Fujii and Ms M Kitazume. This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan; the Intramural Research Fund (27-2-2) for Cardiovascular Diseases of the National Cerebral and Cardiovascular Center of Japan; the Japan Vascular Disease Research Foundation; and the Takeda Scientific Foundation.
About this article
Supplementary Information accompanies this paper on International Journal of Obesity website (http://www.nature.com/ijo)