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

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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.