| First Author | Lin J | Year | 2017 |
| Journal | Mol Med Rep | Volume | 16 |
| Issue | 2 | Pages | 1785-1792 |
| PubMed ID | 28627641 | Mgi Jnum | J:271944 |
| Mgi Id | MGI:6282426 | Doi | 10.3892/mmr.2017.6774 |
| Citation | Lin J, et al. (2017) Osteopontin deficiency protects mice from cholesterol gallstone formation by reducing expression of intestinal NPC1L1. Mol Med Rep 16(2):1785-1792 |
| abstractText | Homeostasis of cholesterol is regulated by absorption in the intestine and synthesis in the liver. The authors previously demonstrated that OPN (osteopontin) exhibits the ability to alter hepatic cholesterol metabolism, thus affecting cholesterol gallstone formation in mice. The present study investigated the role of OPN in cholesterol gallstone formation, focusing on its effect on intestinal absorption of cholesterol. OPN gene knockout (OPN/) mice and wildtype mice were respectively fed with a chow or lithogenic diet (LD) for 8 weeks. Following an 8week LD period, the incidence of gallstone, bile composition, level of serum and fecal lipids and the expression of intestinal associated genes were analyzed. OPN/ mice were protected from gallstone formation induced by 8 weeks' LDfeeding. This protective effect from OPN deficiency was associated with alterations in bile composition, including a reduced concentration of biliary cholesterol. Additionally, plasma cholesterol level was decreased in LDfed OPN/ mice. The alterations primarily resulted from the decreased expression of intestinal NiemannPick C1like (NPC1 L) 1, which is important in the intestinal absorption of cholesterol. The present study demonstrated that OPN deficiency reduced intestinal absorption of cholesterol by suppressing the expression of NPC1L1, thus protecting mice from cholesterol gallstone formation. |
