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.

The Role of the High-Density Lipoprotein Receptor SR-BI in the Lipid Metabolism of Endocrine and Other Tissues

“…This study also demonstrated similar reciprocal changes in parenchymal and Kupffer cell expression after cholesterol feeding (212). However, studies with hamsters and mice did not find that hepatic SR-BI levels and/or HDL cholesteryl ester transport were regulated by changes in dietary cholesterol (237)(238)(239). In addition, a deficiency of plasma HDL in apoA-I KO mice does not increase hepatic SR-BI expression (240).…”

Effects of dietary alpha linolenic acid on cholesterol metabolism in male and female hamsters of the LPN strain

“…Final lipid content of the diet was 14 to 15% and that of CT was Ͻ0.1%. The cholesterol content of the "linseed" diet (0.064%) was not adjusted to that of the "butter" diet (0.097%) because the LPN strain is known to exhibit a low metabolic responsiveness to dietary cholesterol [34]. Moreover, previous studies in the hamster showed that, in this range of cholesterol content, the effects of dietary cholesterol alone are minor in regard to that of the saturated vs. polyunsaturated FA [35,36].…”

Influence of the HDL Receptor SR-BI on Lipoprotein Metabolism and Atherosclerosis

“…34 However, studies with hamsters and mice did not find that hepatic SR-BI levels or HDL cholesteryl ester transport were regulated by changes in dietary cholesterol. [47][48][49] In the liver, a soluble multiple PDZ-domain-containing protein, PDZK1 (also called CLAMP), binds to the cytoplasmic C-terminus of SR-BI 38 and seems to play an important role in controlling the intracellular transport, polarized expression, stability, and activity of SR-BI. 38,50 Coexpression of PDZK1/CLAMP with SR-BI in transfected cells affects both the stability of SR-BI as well as the efficiency of conversion of HDL cholesteryl esters taken up via SR-BI to intracellular unesterified cholesterol.…”