Reduced ileal expression of OSTα-OSTβ in non-obese gallstone disease
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 t...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2008-09-01
|
| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520346721 |
| _version_ | 1819293798674464768 |
|---|---|
| author | Olga Renner Simone Harsch André Strohmeyer Silke Schimmel Eduard F. Stange |
| author_facet | Olga Renner Simone Harsch André Strohmeyer Silke Schimmel Eduard F. Stange |
| author_sort | Olga Renner |
| collection | DOAJ |
| description | 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 α and β (OSTα, OSTβ) in gallstone pathogenesis remains unclear. Therefore, we performed analysis of OSTα-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). OSTα-OSTβ mRNA expression was measured using the LightCycler sequence detection system; protein was analyzed by immunohistochemistry and Western blot. The mRNA expression of OSTα-OSTβ was significantly reduced (OSTα: 3.3-fold, P = 0.006; OSTβ: 2.6-fold, P = 0.03) in normal-weight but not overweight gallstone carriers compared with controls. OSTα-OSTβ protein levels also showed a reduction by 40–67%. The expression of OSTα-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. |
| first_indexed | 2024-12-24T04:16:09Z |
| format | Article |
| id | doaj.art-4219762d2fd04ab2b916d478091a413a |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-24T04:16:09Z |
| publishDate | 2008-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-4219762d2fd04ab2b916d478091a413a2022-12-21T17:15:56ZengElsevierJournal of Lipid Research0022-22752008-09-0149920452054Reduced ileal expression of OSTα-OSTβ in non-obese gallstone diseaseOlga Renner0Simone Harsch1André Strohmeyer2Silke Schimmel3Eduard F. Stange4Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology Stuttgart and University of Tübingen, GermanyDr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology Stuttgart and University of Tübingen, GermanyDr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology Stuttgart and University of Tübingen, GermanyDr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology Stuttgart and University of Tübingen, GermanyDepartment of Internal Medicine I, Robert-Bosch-Hospital, Stuttgart, GermanyCholelithiasis 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 α and β (OSTα, OSTβ) in gallstone pathogenesis remains unclear. Therefore, we performed analysis of OSTα-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). OSTα-OSTβ mRNA expression was measured using the LightCycler sequence detection system; protein was analyzed by immunohistochemistry and Western blot. The mRNA expression of OSTα-OSTβ was significantly reduced (OSTα: 3.3-fold, P = 0.006; OSTβ: 2.6-fold, P = 0.03) in normal-weight but not overweight gallstone carriers compared with controls. OSTα-OSTβ protein levels also showed a reduction by 40–67%. The expression of OSTα-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.http://www.sciencedirect.com/science/article/pii/S0022227520346721gallstonesintestineorganic solute transporters α and βfarnesoid X receptorfibroblast growth factor-19liver receptor homolog-1 |
| spellingShingle | Olga Renner Simone Harsch André Strohmeyer Silke Schimmel Eduard F. Stange Reduced ileal expression of OSTα-OSTβ in non-obese gallstone disease Journal of Lipid Research gallstones intestine organic solute transporters α and β farnesoid X receptor fibroblast growth factor-19 liver receptor homolog-1 |
| title | Reduced ileal expression of OSTα-OSTβ in non-obese gallstone disease |
| title_full | Reduced ileal expression of OSTα-OSTβ in non-obese gallstone disease |
| title_fullStr | Reduced ileal expression of OSTα-OSTβ in non-obese gallstone disease |
| title_full_unstemmed | Reduced ileal expression of OSTα-OSTβ in non-obese gallstone disease |
| title_short | Reduced ileal expression of OSTα-OSTβ in non-obese gallstone disease |
| title_sort | reduced ileal expression of ostα ostβ in non obese gallstone disease |
| topic | gallstones intestine organic solute transporters α and β farnesoid X receptor fibroblast growth factor-19 liver receptor homolog-1 |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520346721 |
| work_keys_str_mv | AT olgarenner reducedilealexpressionofostaostbinnonobesegallstonedisease AT simoneharsch reducedilealexpressionofostaostbinnonobesegallstonedisease AT andrestrohmeyer reducedilealexpressionofostaostbinnonobesegallstonedisease AT silkeschimmel reducedilealexpressionofostaostbinnonobesegallstonedisease AT eduardfstange reducedilealexpressionofostaostbinnonobesegallstonedisease |