Obesity is a growing issue of the modern world, and its negative impact on bones in obese male patients has been recently reported. The Wnt/β-catenin pathway has an established role in the regulation of body fat content and bone density. We investigated the effects of indirubin-3'-oxime (I3O), the GSK3β inhibitor that activates Wnt/β-catenin signaling, on trabecular bone in high-fat diet (HFD)-induced obese male mice. I3O reverses the downregulating effect of fatty acid (FA) on Wnt/β-catenin signaling and enhances the osteogenic commitment of the bone marrow-derived stromal cell line ST2. FA induces the adipogenic differentiation of bone marrow stromal cells in vitro. In a male mouse model of HFD-induced obesity, trabecular bone loss was observed in the femora, with a gross increase in abdominal fat; however, the HFD effects were rescued with the activation of Wnt/β-catenin signaling by I3O treatment. I3O administration also reversed the increase in the number of HFD-induced adipocytes in the femur bone marrow in trabecular bone. Overall, our results indicate that I3O could be a potential therapeutic agent for obese male patients through downregulation of abdominal fat and net increment in trabecular bone density.
Bibliographical noteFunding Information:
This project was partially sponsored by the Mid-career Researcher Program ( 2012R1A2A1A01010285 ), and the Translational Research Center for Protein Function Control ( 2009-0083522 ) of the National Research Foundation (NRF) funded by the Ministry of Science, ICT & Future Planning . This work was also supported by a grant from the Korea Research Institute of Chemical Technology ( SI-095 ). MZ was supported by a BK21 scholarship from the Ministry of Education and Human Resources Development ( 21A20131212313 ).
All Science Journal Classification (ASJC) codes
- Endocrinology, Diabetes and Metabolism