Screening of novel factors for those regulating fat mass under the nutrient excess state

我们最近发现了一种新的信号通路，涉及ALK7，一种I型tgf β受体，通过抑制脂肪分解增加脂肪细胞大小和脂质含量。为了了解这一途径的功能和调控，有必要确定这种孤儿受体的未知配体。为此，我们筛选了33个哺乳动物TGFbeta家族成员在营养过剩状态下的表达上调。结果，四名成员被发现是上调的。其中3个在培养细胞中表现出通过ALK7增加基因表达的配体活性。这三种候选配体在脂肪组织中均有高表达，尽管它们分别在不同种类的细胞中表达。这些结果表明，这些ALK7配体以自分泌或旁分泌的方式调节成熟脂肪细胞的脂质代谢和含量。

We recently discovered a novel signaling pathway involving ALK7, one of the type I TGFbeta receptors, which increases both the adipocyte size and lipid content by suppressing lipolysis. To understand the function and regulation of this pathway, it is essential to identify its unknown ligands of this orphan receptor. For this purpose, 33 mammalian TGFbeta family members were screened for those upregulated under a nutrient excess state. As a result, four members were found to be upregulated. Furthermore, three of them showed ligand activities to increase gene expression through ALK7 in cultured cells. All the three candidate ligands were highly expressed in adipose tissue, although each of them was expressed in different kinds of cells. These results suggest that these ALK7 ligands function in an autocrine or paracrine manner to regulate the lipid metabolism and content of mature adipocytes.