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 wild‑type mice were respectively fed with a chow or lithogenic diet (LD) for 8 weeks. Following an 8‑week 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' LD‑feeding. 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 LD‑fed OPN‑/‑ mice. The alterations primarily resulted from the decreased expression of intestinal Niemann‑Pick C1‑like (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.