Identification of genes specifically expressed in the accumulated visceral adipose tissue of OLETF rats

Kazuyuki Hida, Jun Wada, Hong Zhang, Keita Hiragushi, Yoshinori Tsuchiyama, Kenichi Shikata, Hirofumi Makino

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

The Otsuka Long-Evans Tokushima fatty (OLETF) rat is an animal model of type 2 diabetes, characterized by abdominal obesity, insulin resistance, hypertension, and dyslipidemia. To elucidate the underlying molecular mechanism of obesity and its related complications, we used representational difference analysis and identified the genes more abundantly and specifically expressed 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 confirmed the differential expression of 13 genes, including 3 novel genes. The upregulated expression of well-characterized lipid metabolic enzymes, such as lipoprotein lipase, phosphoenolpyruvate carboxykinase, and cholesterol esterase, were observed in VAT of OLETF rats. We demonstrated the differential expression of secreted proteins in VAT of OLETF rats, such as thrombospondin 1 and contrapsin-like protease inhibitor. In contrast to lipid enzymes, the secreted proteins revealed exclusive mRNA expression and they were not detected in VAT of LETO rats. Furthermore, the novel genes OL-16 and OL-64 were also expressed specifically 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 partial amino acid sequence of OL-64 revealed that it showed ~40% homology with α1-antitrypsin and it seemed to be a new member of the serine proteinase inhibitor (SERPIN) gene family. VAT of OLETF rats had a unique gene expression profile, and the accumulated VAT-specific known and novel secreted proteins may play a role(s) in the pathogenesis of obesity and its related complications.

Original languageEnglish
Pages (from-to)1615-1622
Number of pages8
JournalJournal of Lipid Research
Volume41
Issue number10
Publication statusPublished - Oct 24 2000

Keywords

  • Molecular cloning
  • OLETF rats
  • Obesity
  • PCR-based subtraction method
  • Representational difference analysis
  • Visceral adipose tisssue

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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