Xinzhi Zhang1, Xin Wen1, Geng Hu2, Qiang Zhang1, Qianying Sun1, Yanxin Jia1, Yan Liu1, Hai Lin3, Haifang Li4. 1. State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Tai'an, 271018, China. 2. College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an, 271018, China. 3. College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an, 271018, China. hailin@sdau.edu.cn. 4. State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Tai'an, 271018, China. haifangli@sdau.edu.cn.
Abstract
BACKGROUND: AS an allosteric inhibitor of fibroblast growth factor receptors (FGFRs), SSR128129E (SSR) extensively inhibits the fibroblast growth factor (FGF) signaling. Given the metabolic importance of FGFs and the global epidemic of obesity, we explored the effect of SSR on fat metabolism. METHODS AND RESULTS: Three-week-old male mice were administered intragastrically with SSR (30 mg/kg/day) or PBS for 5 weeks. The effects of SSR on white and brown fat metabolism were investigated by respiratory metabolic monitoring, histological assessment and molecular analysis. Results indicated that SSR administration significantly reduced the body weight gain and the fat content of mice. SSR did not increase, but decreased the thermogenic capability of both brown and white fat. However, SSR markedly suppressed adipogenesis of adipose tissues. Further study demonstrated the involvement of ERK signaling in the action of SSR. CONCLUSIONS: SSR may be a promising drug candidate for the prevention of obesity via suppressing adipogenesis. However, the influence of SSR on thermogenesis in humans should be further investigated before its clinical application.
BACKGROUND: AS an allosteric inhibitor of fibroblast growth factor receptors (FGFRs), SSR128129E (SSR) extensively inhibits the fibroblast growth factor (FGF) signaling. Given the metabolic importance of FGFs and the global epidemic of obesity, we explored the effect of SSR on fat metabolism. METHODS AND RESULTS: Three-week-old male mice were administered intragastrically with SSR (30 mg/kg/day) or PBS for 5 weeks. The effects of SSR on white and brown fat metabolism were investigated by respiratory metabolic monitoring, histological assessment and molecular analysis. Results indicated that SSR administration significantly reduced the body weight gain and the fat content of mice. SSR did not increase, but decreased the thermogenic capability of both brown and white fat. However, SSR markedly suppressed adipogenesis of adipose tissues. Further study demonstrated the involvement of ERK signaling in the action of SSR. CONCLUSIONS: SSR may be a promising drug candidate for the prevention of obesity via suppressing adipogenesis. However, the influence of SSR on thermogenesis in humans should be further investigated before its clinical application.
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