• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>EBioMedicine >Sustained Brown Fat Stimulation and Insulin Sensitization by a Humanized Bispecific Antibody Agonist for Fibroblast Growth Factor Receptor 1/@bKlotho Complex
【24h】

Sustained Brown Fat Stimulation and Insulin Sensitization by a Humanized Bispecific Antibody Agonist for Fibroblast Growth Factor Receptor 1/@bKlotho Complex

机译：持续的棕色脂肪刺激和人源化双特异性抗体激动剂对成纤维细胞生长因子受体1 / @ bKlotho复合物的胰岛素敏感性。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Dissipating excess calories as heat through therapeutic stimulation of brown adipose tissues (BAT) has been proposed as a potential treatment for obesity-linked disorders. Here, we describe the generation of a humanized effector-less bispecific antibody that activates fibroblast growth factor receptor (FGFR) 1/@bKlotho complex, a common receptor for FGF21 and FGF19. Using this molecule, we show that antibody-mediated activation of FGFR1/@bKlotho complex in mice induces sustained energy expenditure in BAT, browning of white adipose tissue, weight loss, and improvements in obesity-associated metabolic derangements including insulin resistance, hyperglycemia, dyslipidemia and hepatosteatosis. In mice and cynomolgus monkeys, FGFR1/@bKlotho activation increased serum high-molecular-weight adiponectin, which appears to contribute over time by enhancing the amplitude of the metabolic benefits. At the same time, insulin sensitization by FGFR1/@bKlotho activation occurs even before the onset of weight loss in a manner that is independent of adiponectin. Together, selective activation of FGFR1/@bKlotho complex with a long acting therapeutic antibody represents an attractive approach for the treatment of type 2 diabetes and other obesity-linked disorders through enhanced energy expenditure, insulin sensitization and induction of high-molecular-weight adiponectin.
机译：通过治疗性刺激棕色脂肪组织（BAT）消散多余的热量作为热量，已被认为是肥胖相关疾病的潜在治疗方法。在这里，我们描述了人源化的少效应双特异性抗体的产生，该抗体可激活成纤维细胞生长因子受体（FGFR）1 / bKlotho复合物，FGF21和FGF19的常见受体。使用该分子，我们显示抗体介导的小鼠FGFR1 / @ bKlotho复合物的激活诱导BAT中持续的能量消耗，白色脂肪组织褐变，体重减轻以及与肥胖相关的代谢紊乱的改善，包括胰岛素抵抗，高血糖，血脂异常和肝脂肪变性。在小鼠和食蟹猴中，FGFR1 / @ bKlotho激活会增加血清高分子量脂联素，这似乎随着时间的推移会通过增加新陈代谢的幅度而起作用。同时，甚至在减肥开始之前，FGFR1 / @ bKlotho激活也会使胰岛素致敏，其方式与脂联素无关。一起，用长效治疗性抗体选择性激活FGFR1 / @ bKlotho复合物代表了一种通过增加能量消耗，胰岛素敏感性和诱导高分子量脂联素来治疗2型糖尿病和其他肥胖相关疾病的诱人方法。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号