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SCFA-GPR43 interactions modulate colitis by regulating inflammatory cytokine production in mononuclear cells.

YANAGIYA, TAKAHIRO, ATSUSHI TANABE, AND KIKUKO HOTTA. Gap-junctional communication is required for mitotic clonal expansion during adipogenesis. Obesity. 2007;15:572-582. Objective: 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 adipogenesis. Research Methods and Procedures: 3T3-L1 preadipocytes were differentiated in the presence of gap junction inhibitor, 18-␣-glycyrrhetinic acid (AGA), and accumulation of cytoplasmic triglycerides was measured. 3T3-L1 cells were transfected with 100 nM small interfering RNA duplexes targeting connexin (Cx) 43. The mRNA levels of CCAAT/ enhancer-binding protein (C/EBP) ␣, peroxisome proliferator-activated receptor ␥, glucose transporter 4, C/EBP␤, and Cx43 were measured by real-time polymerase chain reaction. The protein levels of C/EBP␤ were quantitated by Western blotting. The cell proliferation was measured by counting cell numbers, and DNA synthesis was measured by bromodeoxyuridine incorporation. Results: AGA inhibited adipocyte differentiation dose-dependently. The lipid accumulation and the mRNA levels of C/EBP␣, peroxisome proliferator-activated receptor ␥, and glucose transporter 4 were markedly reduced in AGAtreated adipocytes. The mRNA levels of C/EBP␤ did not decrease; however, C/EBP␤ [liver-enriched transcriptional activator protein (LAP)] expression and the C/EBP␤ (LAP)-to-C/EBP [liver-enriched transcriptional inhibitory protein (LIP)] 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 Cx43. Down-regulation of Cx43 using small interfering RNA reduced the expression of C/EBP␤ (LAP) and inhibited adipogenesis. Discussion: Our data suggest that GJC plays some important roles in adipogenesis through inhibiting mitotic clonal expansion and modulating C/EBP␤ (LAP) expression.

Genetic variations in the SCG3 gene may influence the risk of obesity through possible regulation of hypothalamic neuropeptide secretion.

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