Identification of genes specifically expressed in the accumulated visceraladipose tissue of OLETF rats

The Otsuka Long-Evans Tokushima fatty (OLETF) rat is an animal model of typ e 2 diabetes, characterized by abdominal obesity, insulin resistance, hyper tension, and dyslipidemia. To elucidate the underlying molecular mechanism of obesity and its related complications, we used representational differen ce analysis and identified the genes more abundantly and specifically expre ssed in the visceral adipose tissue (VAT) of obese OLETF rats compared with the diabetes-resistant counterpart, that is, Long Evans Tokushima Otsuka ( LETO) rats. By Northern blot analysis, we con firmed the differential expre ssion of 13 genes, including 3 novel genes. The upregulated expression of w ell-characterized lipid metabolic enzymes, such as lipoprotein lipase, phos phoenolpyruvate carboxykinase, and cholesterol esterase, were observed in V AT of OLETF rats. We demonstrated the differential expression of secreted p roteins in VAT of OLETF rats, such as thrombospondin 1 and contrapsin-like protease inhibitor. In contrast to lipid enzymes, the secreted proteins rev ealed exclusive mRNA expression and they were not detected in VAT of LETO r ats. Furthermore, the novel genes OL-16 and OL-64 were also expressed speci fically in VAT of OLETF rats and were absent in that of LETO rats and other tissues, including subdermal and brown adipose tissues. The C-terminal par tial amino acid sequence of OL-64 revealed that it showed similar to 40% ho mology with alpha(1)-antitrypsin and it seemed to be a new member of the se rine proteinase inhibitor (SERPIN) gem family. VAT of OLETF rats had a uniq ue gem expression profile, and the accumulated VAT-specific known and novel secreted proteins may play a role(s) in the pathogenesis of obesity and it s related complications.