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

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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.