Cholesterol, Bile Acid, And Lipoprotein Metabolism In Two Strains Of Hamster, One Resistant, The Other Sensitive (LPN) To Sucrose-Induced Cholelithiasis

A comprehensive study of cholesterol, bile acid, and lipoprotein metabolism was undertaken in two strains of hamster that differed markedly in their response to a sucrose-rich/low fat diet. Under basal conditions, hamsters from the LPN strain differed from Janvier hamsters by a lower cholesterolemia, a higher postprandial insulinemia, a more active cholesterogenesis in both liver [3- to 4-fold higher 3-hydroxy 3-methylglutaryl coenzyme A reductase (HMG-CoAR) activity and mRNA] and small intestine, and a lower hepatic acyl-coenzyme A:cholesterol acyltransferase activity. Cholesterol saturation indices in the gallbladder bile were similar for both strains, but the lipid concentration was 2-fold higher in LPN than in Janvier hamsters. LPN hamsters had a lower capacity to transform cholesterol into bile acids, shown by the smaller fraction of endogenous cholesterol converted into bile acids prior to fecal excretion (0.34 vs. 0.77). In LPN hamsters, the activities of cholesterol 7 -hydroxylase (C7OHase) and sterol 27-hydroxylase (S27OHase), the two rate-limiting enzymes of bile acid synthesis, were disproportionably lower (by 2-fold) to that of HMG-CoAR. When fed a sucrose-rich diet, plasma lipids increased, dietary cholesterol absorption improved, hepatic activities of HMG-CoA reductase, C7Ohase, and S27OHase were reduced, and intestinal S27OHase was inhibited in both strains. Despite a similar increase in the biliary hydrophobicity index due to the bile acid enrichment in chenodeoxycholic acid and derivatives, only LPN hamsters had an increased lithogenic index and developed cholesterol gallstones (75% incidence), whereas Janvier hamsters formed pigment gallstones (79% incidence). These studies indicate that LPN hamsters have a genetic predisposition to sucrose-induced cholesterol gallstone formation related to differences in cholesterol and bile acid metabolism

Antilithiasic Effect Of Beta-Cyclodextrin In LPN Hamster: Comparison With Cholestyramine

Beta-Cyclodextrin (BCD), a cyclic oligosaccharide that binds cholesterol and bile acids in vitro, has been previously shown to be an effective plasma cholesterol lowering agent in hamsters and domestic pigs. This study examined the effects of BCD as compared with cholestyramine on cholesterol and bile acid metabolism in the LPN hamster model model for cholesterol gallstones. The incidence of cholesterol gallstones was 65% in LPN hamsters fed the lithogenic diet, but decreased linearly with increasing amounts of BCD in the diet to be nil at a dose of 10% BCD. In gallbladder bile, cholesterol, phospholipid and chenodeoxycholate concentrations, hydrophobic and lithogenic indices were all significantly decreased by 10% BCD. Increases in bile acid synthesis (+110%), sterol 27-hydroxylase activity (+106%), and biliary cholate secretion (+140%) were also observed, whereas the biliary secretion of chenodeoxycholate decreased (-43%). The fecal output of chenodeoxycholate and cholate (plus derivatives) was increased by +147 and +64%, respectively, suggesting that BCD reduced the chenodeoxycholate intestinal absorption preferentially. Dietary cholestyramine decreased biliary bile acid concentration and secretion, but dramatically increased the fecal excretion of chenodeoxycholate and cholate plus their derivatives (+328 and +1940%, respectively). In contrast to BCD, the resin increased the lithogenic index in bile, induced black gallstones in 34% of hamsters, and stimulated markedly the activities of HMG-CoA reductase (+670%), sterol 27-hydroxylase (+310%), and cholesterol 7 alpha-hydroxylase (+390%). Thus, beta-cyclodextrin (BCD) prevented cholesterol gallstone formation by decreasing specifically the reabsorption of chenodeoxycholate, stimulating its biosynthesis and favoring its fecal elimination. BCD had a milder effect on lipid metabolism than cholestyramine and does not predispose animals to black gallstones as cholestyramine does in this animal model

KIT is required for hepatic function during mouse post-natal development

<p>Abstract</p> <p>Background</p> <p>The <it>Kit </it>gene encodes a receptor tyrosine kinase involved in various biological processes including melanogenesis, hematopoiesis and gametogenesis in mice and human. A large number of <it>Kit </it>mutants has been described so far showing the pleiotropic phenotypes associated with partial loss-of-function of the gene. Hypomorphic mutations can induce a light coat color phenotype while complete lack of KIT function interferes with embryogenesis. Interestingly several intermediate hypomorphic mutations induced in addition growth retardation and post-natal mortality.</p> <p>Results</p> <p>In this report we investigated the post-natal role of <it>Kit </it>by using a panel of chemically-induced hypomorphic mutations recently isolated in the mouse. We found that, in addition to the classical phenotypes, mutations of <it>Kit </it>induced juvenile steatosis, associated with the downregulation of the three genes, <it>VldlR</it>, <it>Lpin1 </it>and <it>Lpl</it>, controlling lipid metabolism in the post-natal liver. Hence, <it>Kit </it>loss-of-functions mimicked the inactivation of genes controlling the hepatic metabolism of triglycerides, the major source of energy from maternal milk, leading to growth and viability defects during neonatal development.</p> <p>Conclusion</p> <p>This is a first report involving KIT in the control of lipid metabolism in neonates and opening new perspectives for understanding juvenile steatosis. Moreover, it reinforces the role of Kit during development of the liver and underscores the caution that should be exerted in using KIT inhibitors during anti-cancer treatment.</p

Four-week short chain fructo-oligosaccharides ingestion leads to increasing fecal bifidobacteria and cholesterol excretion in healthy elderly volunteers

<p>Abstract</p> <p>Background</p> <p>Short-chain fructo-oligosaccharides (scFOS) are increasingly used in human diet for their prebiotic properties. We aimed at investigating the effects of scFOS ingestion on the colonic microflora and oro-fecal transit time in elderly healthy humans.</p> <p>Methods</p> <p>Stools composition, oro-fecal transit time, and clinical tolerance were evaluated in 12 healthy volunteers, aged 69 ± 2 yrs, in three consecutive periods: basal period (2 weeks), scFOS (Actilight^®) ingestion period (8 g/d for 4 weeks) and follow-up period (4 weeks). Two-way ANOVA, with time and treatment as factors, was used to compare the main outcome measures between the three periods.</p> <p>Results</p> <p>Fecal bifidobacteria counts were significantly increased during the scFOS period (9.17 ± 0.17 log cfu/g vs 8.52 ± 0.26 log cfu/g during the basal period) and returned to their initial values at the end of follow-up (8.37 ± 0.21 log cfu/g; P < 0.05). Fecal cholesterol concentration increased during the scFOS period (8.18 ± 2.37 mg/g dry matter vs 2.81 ± 0.94 mg/g dry matter during the basal period) and returned to the baseline value at the end of follow-up (2.87 ± 0.44 mg/g dry matter; P < 0.05). Fecal pH tended to decrease during scFOS ingestion and follow-up periods compared to the basal period (P = 0.06). Fecal bile acids, stool weight, water percentage, and oro-fecal transit time did not change throughout the study. Excess flatus and bloating were significantly more frequent during scFOS ingestion when compared to the basal period (P < 0.05), but the intensity of these symptoms was very mild.</p> <p>Conclusion</p> <p>Four-week 8 g/d scFOS ingestion is well tolerated and leads to a significant increase in fecal bifidobacteria in healthy elderly subjects. Whether the change in cholesterol metabolism found in our study could exert a beneficial action warrants further studies.</p

Effects of ileo-rectal anastomosis on cholesterol metabolism in pigs fed either casein or extruded soya beans

The importance of legume proteins in the cholesterol metabolism has been recognized in different animals, but the contribution of large intestine to this process is still unclear. The present study was undertaken to compare a casein based diet (C) with a diet, where 60% of the protein supplied by casein was replaced by extruded soybean (ES) on cholesterol metabolism of pigs with (I) and without ileo-rectal anastomosis (IRA). Four groups of six growing pigs (28.0 kg) were assigned to the treatments. All the animals presented a moderate hypercholesterolemia and there were no significant differences, due to the protein source or IRA, in LDL- and HDL- cholesterol plasma concentrations. ES significantly depressed (P0.01) total, free and esters of hepatic cholesterol and increased (P<0.01) hepatic total lipids concentration. There were significant (P<0.05) interactions between diet and IRA on HMG CoA reductase and cholesterol 7- hydroxylase activities, but 27–hydroxylase activity was unaffected. Feeding ES showed a tendency (P=0.056) to decrease the activity of LDL liver receptors, depressed free (P0.05), total cholesterol (P0.01) and total bile acid concentration in bile (P0,001), and increased (P0.05) neutral sterols fecal output. There were interactions effects (P0.05) between diet and IRA in the proportion of microbial sterols, bile acid fecal output and proportion of primary and secondary fecal acids. Nevertheless the effects over hepatic cholesterol and neutral sterol output promoted by ES diets, it wasn’t verified any hypocholesterolemic effect, which could be more related with soybean protein structure and LDL receptors modulation