Regulation of Activin Receptor-like kinase 7 (ALK7) by cGMP in adipocytes

脂肪细胞中 cGMP 对激活素受体样激酶 7 (ALK7) 的调节

• 批准号: 242996745
• 负责人: Professor Dr. Alexander Pfeifer
• 金额: --
• 依托单位: Institut für Pharmakologie und Toxikologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/242996745?language=en
• 关键词: Regulation; Activin; Receptor; like; kinase

In last decades, obesity became a major health issue worldwide affecting more than one billion subjects. Processes as well as molecules involved in fat mass regulation remain largely unresolved up to now. Brown adipose tissue (BAT) is an interesting potential target to fight obesity, because it is capable of disseminating energy as heat (nonshivering thermogenesis). Importantly, in 2009 several groups published that metabolically active BAT is also present in human adults. Since this rediscovery, BAT has gained much interest, which is further intensified by the finding that dissipated brown-like adipocytes (so called beige or brite cells) occur within white adipose tissue (WAT). In this project, we will focus on the activin receptor-like kinase 7 (ALK7), a member of the TGF-beta receptor family. We and others demonstrated that cGMP signaling is essential for the development of both brown and white adipocytes. During a screen for downstream components of the cGMP signaling pathway, we found that cGMP highly regulates expression of ALK7 in brown adipocytes. So far nothing is known about the function of ALK7 in brown adipocytes, our preliminary data indicate that ALK7 plays a role in BAT differentiation. Therefore, we will analyze the function of ALK7 in BAT and WAT, as well as during browning of white adipocytes. Given the crucial role of cGMP signaling in adipogenesis, we will investigate the interaction between the cGMP signaling cascade and ALK7/ TGF-beta /Activin signaling in brown, beige and white adipocytes in vitro and in vivo. Taken together, our aim is to identify not only the function of ALK7 in adipocytes, but also to understand the physiological relevance of the crosstalk between ALK7/ TGF-beta and cGMP signaling.

在过去的几十年里，肥胖成为全球范围内影响超过10亿人的主要健康问题。到目前为止，涉及脂肪质量调节的过程和分子在很大程度上仍未得到解决。棕色脂肪组织（BAT）是对抗肥胖的一个有趣的潜在目标，因为它能够以热量的形式传播能量（非寒颤产热）。重要的是，2009年，几个研究小组发表了代谢活跃的BAT也存在于成人中。自这一重新发现以来，BAT引起了人们极大的兴趣，而在白色脂肪组织（WAT）中发现了消散的棕色样脂肪细胞（所谓的米色或白白色细胞），这进一步加强了人们的兴趣。在这个项目中，我们将重点研究激活素受体样激酶7 (ALK7)，它是tgf - β受体家族的一员。我们和其他人证明了cGMP信号对于棕色和白色脂肪细胞的发育都是必不可少的。在筛选cGMP信号通路下游组分的过程中，我们发现cGMP在棕色脂肪细胞中高度调节ALK7的表达。目前对ALK7在棕色脂肪细胞中的功能尚不清楚，我们的初步数据表明ALK7在BAT分化中起作用。因此，我们将分析ALK7在BAT和WAT以及白色脂肪细胞褐变过程中的作用。鉴于cGMP信号在脂肪形成中的重要作用，我们将在体外和体内研究棕色、米色和白色脂肪细胞中cGMP信号级联与ALK7/ tgf - β /Activin信号的相互作用。综上所述，我们的目的不仅是确定ALK7在脂肪细胞中的功能，而且还了解ALK7/ tgf - β和cGMP信号之间串扰的生理相关性。