Functional analysis of an obesity and diabetes mellitus related novel gene

2005 Fiscal Year Final Research Report Summary

• Project/Area Number: 16590918
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Endocrinology
• Research Institution: RIKEN
• Principal Investigator: HOTTA Kikuko RIKEN, Laboratory for Obesity, Laboratory Head, 肥満関連遺伝子研究チーム, チームリーダー (30360639)
• Co-Investigator(Kenkyū-buntansha): YANAGIYA Takahiro RIKEN, Laboratory for Obesity, Research Scientist, 肥満関連遺伝子研究チーム, 研究員 (40322698)
• Project Period (FY): 2004 – 2005
• Keywords: Adipocyte / Differentiation / Obesity / Connexin 43 / Gap junction

Research Abstract

Gap-junctional communication (GJC) plays critical roles in cell growth and differentiation. Several studies have demonstrated the involvement of GJC in myogenesis and osteogenesis, however, the role of GJC in adipogenesis has not been fully studied. Thus, we investigated the role of GJC in adipocyte differentiation. A gap junction inhibitor, 18-α-glycyrrhetinic acid (AGA), inhibited adipocyte differentiation dose-dependently. The lipid accumulation, and the mRNA levels of C/EBPα, PPARγ and Glut4 were markedly reduced in AGA-treated adipocytes. The mRNA levels of C/EBPβ did not change significantly, however, C/EBPβ (LAP ; liver-enriched transcriptional activator protein) expression and the LAP/LIP (LIP ; liver-enriched transcriptional inhibitory protein) ratio were reduced by AGA treatment. The increase in both cell number and DNA synthesis, which occurs during mitotic clonal expansion, was reduced by AGA in a dose-dependent fashion. The major component of gap junctions in 3T3-L1 cells was connexin 43 (Cx43). Down-regulation of Cx43 using siRNA reduced the expression of C/EBPβ (LAP) and inhibited adipogenesis. Our data suggest that GJC plays several important roles in mitotic clonal expansion and adipogenesis through modulating C/EBPβ (LAP) expression.