A putative white adipose tissue specific nuclear orphan receptor that interacts with the cAMP-response element of the human beta 3-adrenergic receptor gene

The authors previously reported that one of the cAMP-response elements (CRE s) of the human beta 3-AR gene, beta 3CRE2, interacts with a nuclear factor which is distinct from CREB/ATF family. We named this factor WATSF-1 (whit e adipose tissue specific factor-1) since it is preferentially expressed in WAT. In this work, we have shown the absence of DNA binding or transcripti onal activity of this factor in several non-adipose cells tested. By comput er analysis, beta 3CRE2 was found to constitute an octameric element that i s highly homologous to the binding site for some members of the nuclear hor mone receptor superfamily. Using the response elements of other adipocyte-s pecific nuclear receptors as competitors, a 'cross-talk' between WATSF-1 an d these response elements has been demonstrated. However, the affinity of W ATSF-1 for these response elements differs from that for beta 3CRE2 (self), implying that WATSF-1 is distinct from these adipocyte-specific nuclear re ceptors. Furthermore the DNA-binding activity of WATSF-1 was shown to be en hanced by phosphatase treatment; suggesting that phosphorylation may play a n important role in the functional modulation of this factor. In an effort to prove that it is indeed an adipocyte-specific factor, we used 3T3-L1 cel ls, a cellular model of WAT, that can undergo differentiation into adipocyt es. The DNA binding and transcriptional activity of this factor appeared du ring differentiation of the cells. Taken together, these results demonstrat e that WATSF-1 is a putative white adipocyte-specific nuclear orphan recept or induced during adipogenesis and is a transcriptional activator through o ne of the CREs of the human beta 3-AR gene. Targeting this factor may be a novel therapeutic approach to stimulation of the beta 3-AR signal transduct ion pathway in adipose tissues. (C) 2000 Published by Elsevier Science Irel and Ltd. All rights reserved.