Sitosterolemia

Salen, Gerald; Shefer, Sarah; Nguyen, Lien; Ness, Gene C.; Tint, G. S.; Batta, Ashok K.

doi:10.1007/978-1-4615-5901-6_15

Cited by 109 publications

(181 citation statements)

References 39 publications

Supporting

Mentioning

174

Contrasting

Unclassified

Order By: Relevance

“…Reduced hepatic expression of these "sitosterolaemia genes" coincided with a reduction of hepatobiliary cholesterol secretion, whereas their reduced intestinal expression was associated with an increased absorption of cholesterol as deduced from an indirect measure of the process (plasma plant sterol concentrations) and from calculation of the apparent absorption efficiency. Similar changes in cholesterol transport have been reported in sitosterolaemia patients [24] and in Abcg5/Abcg8-deficient mice [8]. Over-expression of the human genes in transgenic mice [7] and pharmacological induction of expression of the endogenous genes in wild-type mice [13] have been reported to have opposite effects, i.e., to stimulate biliary cholesterol excretion and to reduce intestinal cholesterol absorption.…”

Section: Discussionsupporting

confidence: 62%

See 1 more Smart Citation

Down-regulation of hepatic and intestinal Abcg5 and Abcg8 expression associated with altered sterol fluxes in rats with streptozotocin-induced diabetes

Bloks¹,

Waarde²,

Verkade³

et al. 2004

Diabetologia

View full text Add to dashboard Cite

Aim/hypothesis. Type I diabetes is associated with altered hepatic bile formation and increased intestinal cholesterol absorption. The aim of this study was to evaluate whether altered expression of the ATP-Binding Cassette half-transporters Abcg5 and Abcg8, recently implicated in control of both hepatobiliary cholesterol secretion and intestinal cholesterol absorption, contributes to changed cholesterol metabolism in experimental diabetes. Methods. mRNA and protein expression of Abcg5 and Abcg8 were determined in the liver and intestine of rats with streptozotozin-induced diabetes and related to relevant metabolic parameters in plasma, liver and bile. Results. Hepatic mRNA expression of both Abcg5 (−76%) and Abcg8 (−71%) was reduced in diabetic rats when compared to control rats. In spite of increased HDL cholesterol, considered a major source of biliary cholesterol, secretion of the sterol into bile relative to that of bile salts was reduced by 65% in diabetic animals. Intestinal mRNA expression of Abcg5 (−47%) and Abcg8 (−43%) as well as Abcg5 protein contents were also reduced in insulin-deficient animals. This was accompanied by a three-to four-fold increase in plasma β-sitosterol and campesterol concentrations and by a doubling of the calculated apparent cholesterol absorption. These effects partially normalized upon insulin supplementation. Conclusion/interpretation. Our data indicate that effects of insulin-deficiency on bile composition and cholesterol absorption in rats are, at least partly, attributable to changes in hepatic and intestinal Abcg5 and Abcg8 expression. [Diabetologia (2004) Type I diabetes mellitus is associated with specific changes in cholesterol metabolism in humans [1] and in experimental animals [2,3], including increased concentrations of plasma cholesterol, enhanced conversion of cholesterol into bile salts and an enhanced intestinal cholesterol absorption. The hepatobiliary pathway is of crucial importance for the maintenance of cholesterol homeostasis [4]. Bile salts that are secreted by the liver into the intestinal lumen are required for intestinal absorption of dietary cholesterol. The majority of bile salts is subsequently reabsorbed from the intestine and returns to the liver for re-secretion into the bile. The relatively small fraction of bile salts that escapes intestinal absorption is compensated for by de novo synthesis from cholesterol in the liver. Secondly, bile contains considerable amounts of free cholesterol. Since only a part of biliary cholesterol is reabsorbed from the intestine [5], the biliary pathway contributes to a major extent to cholesterol turnover. It is well-established that

show abstract

Section: Discussionsupporting

confidence: 62%

“…Patients with this disease develop xanthomas and premature atherosclerosis [24,25]. Affected individuals show high concentrations of plant sterols in plasma due to the fact that, in contrast to healthy subjects, they efficiently absorb these sterols from the intestine and are unable to excrete them into the bile [24,26].…”

Section: Discussionmentioning

confidence: 99%

Down-regulation of hepatic and intestinal Abcg5 and Abcg8 expression associated with altered sterol fluxes in rats with streptozotocin-induced diabetes

Bloks¹,

Waarde²,

Verkade³

et al. 2004

Diabetologia

View full text Add to dashboard Cite

show abstract

“…The molecular basis for this disease is a defect in both the alleles of either ABCG5 or ABCG8 (reviewed in Lee et al, 2001) that leads to a distinctly increased absorption and reduced biliary excretion of plant sterols (Salen et al, 2000;Lee et al, 2001). Total serum plant sterol concentrations are much higher in affected patients than in controls and range from about 500 to 2250 mmol/l (Salen et al, 1992a). Clinically, most patients are characterized by typically located xanthomas, and many also suffer from markedly augmented atherosclerosis that frequently leads to fatal cardiovascular events very early in life (Salen et al, 1992a).…”

Section: Introductionmentioning

confidence: 99%

“…Total serum plant sterol concentrations are much higher in affected patients than in controls and range from about 500 to 2250 mmol/l (Salen et al, 1992a). Clinically, most patients are characterized by typically located xanthomas, and many also suffer from markedly augmented atherosclerosis that frequently leads to fatal cardiovascular events very early in life (Salen et al, 1992a).…”

Section: Introductionmentioning

confidence: 99%

Similar serum plant sterol responses of human subjects heterozygous for a mutation causing sitosterolemia and controls to diets enriched in plant sterols or stanols

et al. 2007

View full text Add to dashboard Cite

Objective: We investigated the serum phytosterol responses of heterozygous relatives of sitosterolemia patients to diets enriched in phytosterols or stanols. Design: Randomized double-blind crossover design. Setting: Muenster, Germany. Subjects: Eight heterozygous and 13 control subjects were recruited. One heterozygote and three controls dropped out. Interventions: Seven heterozygotes and 10 controls received daily portions of margarine containing 2 g of plant sterols, 2 g of stanols or a control margarine for 6 weeks each in a randomized order. These phases were intercepted by wash-out periods of 6 weeks each. Results: Compared to the control period, serum phytosterol concentrations increased overall by more than 20% when subjects consumed the plant sterol margarine (F (1,15) ¼ 8.719, P ¼ 0.01), with no significant difference between heterozygotes (mean þ 14.5 (s.d. 17.2) mmol/l, þ 23.0%) and controls ( þ 4.9 (9.9) mmol/l, þ 20.5%; F (1,15) ¼ 2.168, P ¼ 0.162), but decreased when subjects consumed the stanol-enriched margarine (F (1,15) ¼ 12.124, P ¼ 0.003), again to a similar extent in heterozygotes (À34.2 (41.2) mmol/l, À54.2%) and controls (À12.2 (9.2) mmol/l, À50.6%; F (1,15) ¼ 2.729, P ¼ 0.119). The lowest total serum concentrations of cholesterol and phytosterols were seen after the diet enriched in stanols. Serum stanol concentrations increased on this diet, but on a very low level and never exceeded 0.05% of serum cholesterol levels in any subject. Conclusions: Serum phytosterol concentrations increased only moderately in heterozygotes consuming a diet enriched in phytosterols, indicating that they retained considerable capacity to excrete phytosterols even at higher intakes. Sponsorship: Supported by a grant of the Stifterverband für die Deutsche Wissenschaft (project number TS022/12372/2002) to MK.

show abstract

“…5,6 In addition, some patients can present with haematological abnormalities including macrothrombocytopenia, stomatocytes, haemolytic anaemia and splenomegaly. 7,8 Very rare patients can present primarily with elevated plasma levels of lowdensity lipoprotein cholesterol and cutaneous xanthomas, expressing a phenotype that resembles heterozygous familial hypercholesterolaemia (FH), 9 and in severe cases, resembling homozygous FH, with coronary disease in childhood and adolescence.…”

Section: Clinical Sensitivity (Proportion Of Positive Tests If the DImentioning

confidence: 99%

Clinical utility gene card for: Sitosterolaemia

et al. 2016

View full text Add to dashboard Cite

Sitosterolemia

Cited by 109 publications

References 39 publications

Down-regulation of hepatic and intestinal Abcg5 and Abcg8 expression associated with altered sterol fluxes in rats with streptozotocin-induced diabetes

Down-regulation of hepatic and intestinal Abcg5 and Abcg8 expression associated with altered sterol fluxes in rats with streptozotocin-induced diabetes

Similar serum plant sterol responses of human subjects heterozygous for a mutation causing sitosterolemia and controls to diets enriched in plant sterols or stanols

Clinical utility gene card for: Sitosterolaemia

Contact Info

Product

Resources

About