Decreased hepatic expression of PPAR-γ coactivator-1 in cholesterol cholelithiasis

Authors


  • Dipartimento di Medicine e Specialità Mediche (M. Bertolotti, C. Gabbi, C. Anzivino, M. Ricchi, L. Carulli, P. Loria, N. Carulli), Dipartimento di Scienze Chirurgiche, (A. Rossi), Università degli Studi di Modena e Reggio Emilia; Istituto di Scienze Farmacologiche, Università degli Studi di Milano (N. Mitro, C. Godio, E. De Fabiani, M. Crestani); Dipartimento di Medicina Sperimentale, Ambientale e Biotecnologie, Università degli Studi di Milano Bicocca (M. Del Puppo), Italy.

Marco Bertolotti, md, Dipartimento di Medicine e Specialità Mediche, Divisione di Medicina 3, Policlinico, via del Pozzo 71, 41100 Modena, Italy. Tel.: +39 059422–5583; fax: +39 059363114; e-mail: bertolotti.marco@unimore.it

Abstract

Background  Cholesterol cholelithiasis (gallstone disease) is a common disease in the Western world. The aim of the present study was to analyze the hepatic expression of a number of nuclear receptors involved in bile acid metabolism in human cholesterol gallstone disease.

Materials and methods  Surgical liver biopsies were obtained from 11 patients with untreated cholesterol cholelithiasis and nine gallstone-free subjects; mRNA levels of cholesterol 7α-hydroxylase (CYP7A1) and related nuclear receptors and coactivators were assayed by quantitative real-time RT-PCR.

Results  No differences between the two groups were detected in mRNA levels of CYP7A1 and related nuclear receptors, with the exception of peroxysome proliferator-activated receptor-γ coactivator 1 (PGC-1), which was significantly (P < 0·01) less expressed in gallstone subjects. Expression of PGC-1 was linearly correlated with farnesoid X receptor (FXR) in gallstone patients (r = 0·87 on a log scale, P < 0·01), but not in control subjects; in gallstone patients PGC-1 expression was also correlated with hepatocyte nuclear factor 4 (HNF-4) (r = 0·78, P < 0·01).

Conclusion  These findings suggest that PGC-1 can play a role in the prevention of cholesterol gallstone disease in humans; this might take place via interaction with the bile acid receptor FXR, whose protective role in cholelithiasis has been suggested by recent evidence in animal models and other coactivators. The present data might help to understand the pathophysiology and possibly focus on new therapeutical targets in cholesterol gallstone disease.

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