Abstracts Poster Abstracts - Dr Falk

33Reduced hepatic expression of PPAR-gamma coactivator 1(PGC-1) in human cholelithiasisC. Gabbi, M. Bertolotti, C. Anzivino, N. Mitro*, C. Godio*, E. De Fabiani*, M. Crestani*,L. Carulli, A. Rossi, P. Loria, N. CarulliUniversity of Modena and Reggio Emilia, *University of Milan, ItalyIntroduction: the prevalence of cholesterol cholelithiasis in the Western world is high.Even if laparoscopic cholecystectomy represents a satisfactory treatment in mostinstances, some drawbacks need to be considered such as stone recurrence,pancreatitis due to biliary sludge and postoperative complications. Further insight in thepathophysiology and molecular regulation of biliary lipid secretion is therefore highlydesirable.Aim of the present study was to analyze the hepatic expression of a number of nuclearreceptors involved in bile acid metabolism in human cholelithiasis.Methods: surgical liver biopsies were obtained in 11 patients with untreated cholesterolcholelithiasis and 9 gallstone-free subjects; mRNA levels of CYP7A1 and relatednuclear receptors and coactivators were assayed by real-time quantitative RT-PCR.Results: No differences between the two groups were detected in gene expression ofCYP7A1 and other nuclear receptors, with the exception of PGC-1 which wassignificantly (p < 0.01 on a log scale) less expressed in gallstone subjects. Expressionof PGC-1 was linearly correlated with FXR both in the whole population (r = 0.55 on alog scale, p < 0.05) and in gallstone patients (r = 0.87, p < 0.01); in gallstone patientsPGC-1 expression was also correlated with HNF-4 (r = 0.78, p < 0.01).Discussion/Conclusion: PGC-1 appears to play a role in the prevention of cholesterolgallstone disease in humans; this might take place via interaction with the bile acidreceptor FXR, whose protective role in cholelithiasis has been suggested by recentevidence in animal models. Involvement of target genes coding for biliary lipidtransporters is likely. PGC-1 and related genes might therefore represent moleculartargets for the prevention and/or treatment of gallstone disease.GRANT SUPPORT. Supported by 5 th Framework Program grant QLGI-CT-2001-01513and by COFIN-PRIN grant 2002062991.