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Journal of Lipid Research, Vol. 49, 2045-2054, September 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

Patient-Oriented and Epidemiological Research

Reduced ileal expression of OST-OSTβ in non-obese gallstone disease

Olga Renner^*, Simone Harsch^*, André Strohmeyer^*, Silke Schimmel^* and Eduard F. Stange^1,

^* Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology Stuttgart and University of Tübingen, Germany
Department of Internal Medicine I, Robert-Bosch-Hospital, Stuttgart, Germany

Published, JLR Papers in Press, May 9, 2008.

This study was supported by the Robert Bosch Foundation, Stuttgart.

¹ To whom correspondence should be addressed. e-mail: eduard.stange{at}rbk.de

Cholelithiasis is a multifactorial process, and several mechanisms have been postulated. A decreased expression of the ileal apical sodium-dependent bile acid transporter (ASBT) and of the cytosolic ileal lipid binding protein (ILBP) was recently described in female non-obese patients. The role of the recently identified organic solute transporters and β (OST, OSTβ) in gallstone pathogenesis remains unclear. Therefore, we performed analysis of OST-OSTβ in gallstone patients according to body weight. Ileal mucosal biopsies were collected during routine colonoscopy from female gallstone carriers (n = 19) and controls (n = 34). OST-OSTβ mRNA expression was measured using the LightCycler sequence detection system; protein was analyzed by immunohistochemistry and Western blot. The mRNA expression of OST-OSTβ was significantly reduced (OST: 3.3-fold, P = 0.006; OSTβ: 2.6-fold, P = 0.03) in normal-weight but not overweight gallstone carriers compared with controls. OST-OSTβ protein levels also showed a reduction by 40–67%. The expression of OST-OSTβ correlated positively with ASBT (r = 0.65, 0.58, respectively), ILBP (r = 0.77, 0.67), and the farnesoid X receptor (r = 0.58, 0.50). Fibroblast growth factor-19 showed a 2.8-fold reduction (P = 0.06), and liver receptor homolog-1 showed a 2-fold reduction (P = 0.04) in non-obese patients. In conclusion, an impaired function of all three ileal bile acid transporters may lead to low ileal bile acid reabsorption and an altered bile acid pool composition and therefore may contribute to the formation of gallstones in non-obese patients.

Supplementary key words gallstones • intestine • organic solute transporters and β • farnesoid X receptor • fibroblast growth factor-19 • liver receptor homolog-1

Abbreviations: ASBT, apical sodium-dependent bile acid transporter; FGF-19, fibroblast growth factor-19; FXR, farnesoid X receptor; HNF1, hepatic nuclear factor 1 ; ILBP, ileal lipid binding protein; LRH-1, liver receptor homolog-1; OST, organic solute transporter ; QRT-PCR, quantitative RT-PCR; RAR/RXR, retinoic acid receptor/retinoid X receptor; SHP, short heteromeric partner

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