J Hino1, M Nakatani2, Y Arai3, K Tsuchida2, M Shirai4, M Miyazato1, K Kangawa1. 1. Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan. 2. Division for Therapies against Intractable Diseases, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Japan. 3. Department of Bioscience and Genetics, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan. 4. Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: These results provide in vivo evidence that BMP-3b regulates adipocyte function to cause an anti-obesity effect.
BACKGROUND: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. METHODS: 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. RESULTS: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. CONCLUSIONS: These results provide in vivo evidence that BMP-3b regulates adipocyte function to cause an anti-obesity effect.
Authors: J Hino; M Takao; N Takeshita; Y Konno; T Nishizawa; H Matsuo; K Kangawa Journal: Biochem Biophys Res Commun Date: 1996-06-14 Impact factor: 3.575
Authors: M Takao; J Hino; N Takeshita; Y Konno; T Nishizawa; H Matsuo; K Kangawa Journal: Biochem Biophys Res Commun Date: 1996-02-15 Impact factor: 3.575
Authors: Khrystyna Platko; Paul F Lebeau; Jae Hyun Byun; Samantha V Poon; Emily A Day; Melissa E MacDonald; Nicholas Holzapfel; Aurora Mejia-Benitez; Kenneth N Maclean; Joan C Krepinsky; Richard C Austin Journal: Mol Metab Date: 2019-06-28 Impact factor: 7.422