title: Hamsters predisposed to sucrose-induced cholesterol gallstones (LPN strain) are more resistant to excess dietary cholesterol than hamsters that are not sensitive to cholelithiasis induction.
abstract: We compared the effects of cholesterol feeding in male hamsters from two strains with different propensities to sucrose-induced cholelithiasis; Laboratoire de Physiologie de la Nutrition (LPN) hamsters are predisposed to developing biliary cholesterol gallstones, whereas Janvier (JAN) hamsters are not. When fed a basal control diet, LPN hamsters had a lower cholesterolemia (-21%, P = 0.01) than JAN hamsters, and a higher activity of 3-hydroxy-3-methyl glutaryl coenzyme A reductase in liver (+148%, P = 0.018) and intestine (+281%, P < 0.0001). After feeding the same diet enriched with 0.3% cholesterol for 5 wk, cholesterolemia increased more dramatically in JAN hamsters (+235%, P < 0.001) than in LPN hamsters (+108%, P < 0.001), as did the liver concentration of cholesterol, which reached 152.30 +/- 13.00 and 44.41 +/- 9.06 micromol/g, respectively. Only JAN hamsters displayed hepatomegaly, with an increased cholesterol saturation index of the gallbladder bile (+100%, P < 0.01), due to the cholesterol challenge. In liver, cholesterol feeding reduced cholesterol 7alpha-hydroxylase activity and mRNA level, and stimulated sterol 27-hydroxylase and oxysterol 7alpha-hydroxylase activities. Hepatic levels of LDL receptor decreased by approximately 60% in both strains, whereas HDL receptor scavenger class B type 1 (SR-BI) levels were unaffected by dietary cholesterol. The greater resistance of LPN hamsters to the hypercholesterolemic diet can be explained by a lower capacity to store cholesterol in the liver and greater efficiency in reducing the activity of 3-hydroxy-3-methyl glutaryl coenzyme A reductase in response to cholesterol feeding [from 11263 to 261 pmol/(min x organ) in LPN hamsters and from 4530 to 694 pmol/(min x organ) in JAN hamsters]. These results highlight the usefulness of this two-strain model, which offers some analogy with the inverse association between the predisposition to cholelithiasis and the risk of atherosclerosis in humans.
authors.affiliation: Laboratoire de Physiologie de la Nutrition-INRA, Université Paris XI, F-91405 Orsay Cedex, France.
authors.forename: M
authors.initials: M
authors.lastname: Souidi
authors.forename: M
authors.initials: M
authors.lastname: Combettes-Souverain
authors.forename: F
authors.initials: F
authors.lastname: Milliat
authors.forename: E R
authors.initials: ER
authors.lastname: Eckhardt
authors.forename: O
authors.initials: O
authors.lastname: Audas
authors.forename: S
authors.initials: S
authors.lastname: Dubrac
authors.forename: M
authors.initials: M
authors.lastname: Parquet
authors.forename: J
authors.initials: J
authors.lastname: Férézou
authors.forename: C
authors.initials: C
authors.lastname: Lutton
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000096:biosynthesis; D001835:Body Weight; D002769:Cholelithiasis / Q000139:chemically induced*; D053493:Cholestanetriol 26-Monooxygenase; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D006224:Cricetinae; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004351:Drug Resistance; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D008055:Lipids / Q000032:analysis / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D009929:Organ Size; D012333:RNA, Messenger / Q000032:analysis; D011973:Receptors, LDL / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000378:metabolism; D013395:Sucrose
chemical_list: D001647:Bile Acids and Salts; D002791:Cholesterol, Dietary; D008055:Lipids; D012333:RNA, Messenger; D011973:Receptors, LDL; D013395:Sucrose; D003577:Cytochrome P-450 Enzyme System; D006903:Hydroxymethylglutaryl CoA Reductases; D013250:Steroid Hydroxylases; D002790:Cholesterol 7-alpha-Hydroxylase; D053493:Cholestanetriol 26-Monooxygenase