2003-P: The Role of Re1-Silencing Transcription Factor (REST) in Adipocytes

We have reported that several neuronal genes, glutamate receptor 7 and synuclein γ, are expressed in adipocytes. Since the individual roles of these neuronal genes are different, it is unlikely that these genes carry out any common functions together. Numerous neuronal genes are negatively regulated by REST. Therefore, we generated the mice lacking REST in adipocytes to investigate the role of these genes. Rest2lox/2lox mice were mated with Adipoq-Cre mice, and the resultant Adipoq-Cre/Rest2lox/2lox mice were compared with Adipoq-Cre mice. Male Adipoq-Cre/Rest2lox/2lox mice exceeding 10 weeks of age showed increased body weight and fat mass. There was no difference in food consumption, glucose tolerance evaluated by intraperitoneal GTT (ip-GTT) and adipocyte size. However, glucose tolerance was deteriorated in Adipoq-Cre/Rest2lox/2lox mice after treated with high fat diet (HFD) for 8 weeks. The characteristics of gene expression in epididymal fat isolated from Adipoq-Cre/Rest2lox/2lox mice was examined with microarray with Adipoq-Cre/Rest2lox/2lox mice as a control. Significant increased mRNA levels were detected numerous neuronal genes such as Gdap1, Nrxn1, Nrsn1 and Syn1, in Adipoq-Cre/Rest2lox/2lox mice. In addition, expression of several oncogenes, including Srrm3, Lhfpl5, Stmn3 and Chga (a marker of neuro-endocrine tumor such as pheochromocytoma) were increased in these mice. On the other hand, brown adipose tissue (BAT) in Adipoq-Cre/Rest2lox/2lox mice showed white adipose tissue (WAT)-like appearance. These results suggested that REST might regulate adipocyte differentiation and function in both WAT and BAT. Disclosure M. Fuwa: None. K. Kajita: None. K. Taguchi: None. Y. Kitada: None. T. Ikeda: None. T. Ishizuka: None. H. Morita: None.