scholarly journals Influence of Chitosan Treatment on Surrogate Serum Markers of Cholesterol Metabolism in Obese Subjects

2018 ◽  
Author(s):  
Dieter Lütjohann ◽  
Milka Marinova ◽  
Karsten Wolter ◽  
Winfried Willinek ◽  
Norman Bitterlich ◽  
...  
Keyword(s):  
Bile Acid ◽  
Ldl Cholesterol ◽  
Cholesterol Metabolism ◽  
Cholesterol Absorption ◽  
Acid Synthesis ◽  
Placebo Treatment ◽  
Bile Acid Synthesis ◽  
Cholesterol Concentration ◽  
Surrogate Markers ◽  
Obese Subjects

Chitosan treatment results in significantly lower serum LDL cholesterol concentrations. To assess the working mechanism of chitosan, we measured serum surrogate markers of cholesterol absorption (campesterol, sitosterol, cholestanol), synthesis (lathosterol, lanosterol, desmosterol), and degradation to bile acids (7α-hydroxy-cholesterol, 27-hydroxy-cholesterol) corrected for cholesterol concentration (R_sterols). Over 12 weeks, 116 obese subjects (BMI 31.7, range 28.1 – 38.9 kg/m2) were studied under chitosan (n=61) and placebo treatment (n=55). The participants were briefly educated regarding improvement of nutrition quality and energy expenditure. Daily chitosan intake was 3200 mg. Serum LDL cholesterol concentration decreased significantly more (P=0.0252) under chitosan (-8.67 ± 18.18 mg/dl, 5.6%) than under placebo treatment (-1.00 ± 24.22 mg/dl, 0.9%). This reduction was not associated with the expected greater decreases in markers of cholesterol absorption under chitosan treatment. Also, increase in markers of cholesterol synthesis and bile acid synthesis under chitosan treatment was not any greater than under placebo treatment. In conclusion, a significant selective reduction of serum LDL cholesterol under chitosan treatment is neither associated with a reduction of serum surrogate markers of cholesterol absorption nor with an increases of markers for cholesterol and bile acid synthesis.

scholarly journals Influence of Chitosan Treatment in Obese Subjects on Surrogate Plasma Markers of Cholesterol Metabolism

2018 ◽  
Author(s):  
Dieter Lütjohann ◽  
Milka Marinova ◽  
Karsten Wolter ◽  
Winfried Willinek ◽  
Norman Bitterlich ◽  
...  
Keyword(s):  
Bile Acid ◽  
Ldl Cholesterol ◽  
Cholesterol Metabolism ◽  
Cholesterol Absorption ◽  
Acid Synthesis ◽  
Placebo Treatment ◽  
Bile Acid Synthesis ◽  
Cholesterol Concentration ◽  
Surrogate Markers ◽  
Obese Subjects

Chitosan treatment results in significantly lower plasma LDL-cholesterol concentrations. To test the working mechanism of Chitosan, we measured plasma surrogate markers of cholesterol absorption, synthesis, and degradation to bile acids corrected for cholesterol concentration (R_sterols). One hundred sixteen obese subjects (BMI 31.7, range 28.1 – 38.9 kg/m2) were studied under Chitosan treatment (n=61) and placebo treatment (n=55) during 12 weeks. The participants underwent a short nutrition education on how to improve quality of nutrition and energy expenditure. Daily Chitosan intake was 3200 mg. RESULTS. Plasma LDL-cholesterol concentration decreased significantly stronger (P=0.0252) under Chitosan (-8.67 ± 18.18 mg/dl, 5.6%) than under placebo treatment (-1.00 ± 24.22 mg/dl, 0.9%). This reduction was not associated with corresponding decreases of markers of cholesterol absorption under Chitosan treatment. As a marker for cholesterol synthesis R_lathosterol showed a trend towards a stronger decrease under Chitosan treatment (P=0.0759). Regarding markers of bile acid synthesis, R_7α-hydroxy-cholesterol decreased significantly only under Chitosan treatment, but not stronger than under placebo treatment. In conclusion, a significant selective reduction of plasma LDL-cholesterol under Chitosan treatment is neither associated with an expected reduction of plasma surrogate markers of cholesterol absorption nor with expected increases of markers for cholesterol and bile acid synthesis.

scholarly journals Effects of long-term plant sterol or stanol ester consumption on lipid and lipoprotein metabolism in subjects on statin treatment

2008 ◽  
Vol 100 (5) ◽  
pp. 937-941 ◽  
Author(s):  
Ariënne de Jong ◽  
Jogchum Plat ◽  
Dieter Lütjohann ◽  
Ronald P. Mensink
Keyword(s):  
Bile Acid ◽  
Plant Sterol ◽  
Ldl Cholesterol ◽  
Cholesterol Metabolism ◽  
Acid Synthesis ◽  
Statin Treatment ◽  
Bile Acid Synthesis ◽  
Control Group ◽  
Stanol Ester

Consumption of plant sterol- or stanol-enriched margarines by statin users results in an additional LDL-cholesterol reduction of approximately 10 %, which may be larger than the average decrease of 3–7 % achieved by doubling the statin dose. However, whether this effect persists in the long term is not known. Therefore, we examined in patients already on stable statin treatment the effects of 85 weeks of plant sterol and stanol ester consumption on the serum lipoprotein profile, cholesterol metabolism, and bile acid synthesis. For this, a double-blind randomised trial was designed in which fifty-four patients consumed a control margarine with no added plant sterols or stanols for 5 weeks (run-in period). For the next 85 weeks, seventeen subjects continued with the control margarine and the other two groups with either a plant sterol (n18) or plant stanol (n19) (2·5 g/d each) ester-enriched margarine. Blood was sampled at the end of the run-in period and every 20 weeks during the intervention period. Compared with the control group, plant sterol and stanol ester consumption reduced LDL-cholesterol by 0·28 mmol/l (or 8·7 %;P = 0·08) and 0·42 mmol/l (13·1 %;P = 0·006) respectively after 85 weeks. No effects were found on plasma concentrations of oxysterols or 7α-hydroxy-4-cholesten-3-one, a bile acid synthesis marker. We conclude that long-term consumption of both plant sterol and stanol esters effectively lowered LDL-cholesterol concentrations in statin users.

Common polymorphisms in the CYP7A1 gene do not contribute to variation in rates of bile acid synthesis and plasma LDL cholesterol concentration

2005 ◽  
Vol 182 (1) ◽  
pp. 37-45 ◽  
Author(s):  
Anna Abrahamsson ◽  
Sergey Krapivner ◽  
Ulf Gustafsson ◽  
Olle Muhrbeck ◽  
Gösta Eggertsen ◽  
...  
Keyword(s):  
Bile Acid ◽  
Ldl Cholesterol ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Cholesterol Concentration

scholarly journals Effect of long term simvastatin administration as an adjunct to ursodeoxycholic acid: evidence for a synergistic effect on biliary bile acid composition but not on serum lipids in humans

Gut ◽  
1999 ◽  
Vol 44 (4) ◽  
pp. 552-556 ◽  
Author(s):  
F Lanzarotto ◽  
B Panarotto ◽  
R Sorbara ◽  
M Panteghini ◽  
F Pagani ◽  
...  
Keyword(s):  
Bile Acid ◽  
Synergistic Effect ◽  
Ursodeoxycholic Acid ◽  
Acid Composition ◽  
Ldl Cholesterol ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Cholesterol Concentration ◽  
Biliary Cholesterol ◽  
Biliary Bile Acid

BACKGROUNDStimulated bile acid synthesis preferentially utilises newly synthesised cholesterol, raising the posssiblity that combination of simvastatin (an inhibitor of cholesterol synthesis) with ursodeoxycholic acid (UDCA; a stimulator of bile acid synthesis) may result in reduced bile acid synthesis and greater enrichment of the pool with UDCA than that achieved with UDCA treatment alone.AIMSTo investigate the effect of simvastatin and UDCA given alone and in combination on serum and biliary lipid and biliary bile acid composition.METHODSEighteen patients with primary non-familial hypercholesterolaemia were studied during treatment with simvastatin 20 mg/day, UDCA 10 mg/kg/day, and a combination of the two drugs. Each regimen was given in random order for three months following a three month lead in period.RESULTSSimvastatin significantly reduced serum low density lipoprotein (LDL) cholesterol but biliary cholesterol concentration remained unchanged. Combination of the two drugs had no synergistic effect on serum cholesterol concentration, but significantly increased the proportion of UDCA in the bile acid pool from 35% during UDCA to 48% during combination treatment (p<0.04).CONCLUSIONSResults showed that: (1) simvastatin reduces serum LDL cholesterol but has no effect on biliary cholesterol concentration, supporting the concept that newly synthesised cholesterol is not the preferential source for biliary cholesterol; and (2) combination of simvastatin with UDCA has the predicted effect of enhancing the proportion of UDCA in the pool. This effect may be of benefit in the treatment of cholestatic liver diseases.

scholarly journals Endogenous Estrogens Lower Plasma PCSK9 and LDL Cholesterol But Not Lp(a) or Bile Acid Synthesis in Women

2012 ◽  
Vol 32 (3) ◽  
pp. 810-814 ◽  
Author(s):  
Lena Persson ◽  
Peter Henriksson ◽  
Eli Westerlund ◽  
Outi Hovatta ◽  
Bo Angelin ◽  
...  
Keyword(s):  
Bile Acid ◽  
Ldl Cholesterol ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Lower Plasma

scholarly journals Liver Bile Acid Changes in Mouse Models of Alzheimer’s Disease

2021 ◽  
Vol 22 (14) ◽  
pp. 7451
Author(s):  
Harpreet Kaur ◽  
Drew Seeger ◽  
Svetlana Golovko ◽  
Mikhail Golovko ◽  
Colin Kelly Combs
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Bile Acid ◽  
Bile Acids ◽  
Cholesterol Metabolism ◽  
Amyloid Β ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Liver Cholesterol ◽  
Bile Acid Metabolism

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive cognitive impairment. It is hypothesized to develop due to the dysfunction of two major proteins, amyloid-β (Aβ) and microtubule-associated protein, tau. Evidence supports the involvement of cholesterol changes in both the generation and deposition of Aβ. This study was performed to better understand the role of liver cholesterol and bile acid metabolism in the pathophysiology of AD. We used male and female wild-type control (C57BL/6J) mice to compare to two well-characterized amyloidosis models of AD, APP/PS1, and AppNL-G-F. Both conjugated and unconjugated primary and secondary bile acids were quantified using UPLC-MS/MS from livers of control and AD mice. We also measured cholesterol and its metabolites and identified changes in levels of proteins associated with bile acid synthesis and signaling. We observed sex differences in liver cholesterol levels accompanied by differences in levels of synthesis intermediates and conjugated and unconjugated liver primary bile acids in both APP/PS1 and AppNL-G-F mice when compared to controls. Our data revealed fundamental deficiencies in cholesterol metabolism and bile acid synthesis in the livers of two different AD mouse lines. These findings strengthen the involvement of liver metabolism in the pathophysiology of AD.

scholarly journals Regulation of Bile Acid and Cholesterol Metabolism by PPARs

PPAR Research ◽  
2009 ◽  
Vol 2009 ◽  
pp. 1-15 ◽  
Author(s):  
Tiangang Li ◽  
John Y. L. Chiang
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Cholesterol Metabolism ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Cholesterol Homeostasis ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Major Pathway ◽  
Therapeutic Implications

Bile acids are amphipathic molecules synthesized from cholesterol in the liver. Bile acid synthesis is a major pathway for hepatic cholesterol catabolism. Bile acid synthesis generates bile flow which is important for biliary secretion of free cholesterol, endogenous metabolites, and xenobiotics. Bile acids are biological detergents that facilitate intestinal absorption of lipids and fat-soluble vitamins. Recent studies suggest that bile acids are important metabolic regulators of lipid, glucose, and energy homeostasis. Agonists of peroxisome proliferator-activated receptors (PPARα, PPARγ, PPARδ) regulate lipoprotein metabolism, fatty acid oxidation, glucose homeostasis and inflammation, and therefore are used as anti-diabetic drugs for treatment of dyslipidemia and insulin insistence. Recent studies have shown that activation of PPARαalters bile acid synthesis, conjugation, and transport, and also cholesterol synthesis, absorption and reverse cholesterol transport. This review will focus on the roles of PPARs in the regulation of pathways in bile acid and cholesterol homeostasis, and the therapeutic implications of using PPAR agonists for the treatment of metabolic syndrome.

Abstract 49: The Transcriptional Repressor MafG Regulates Cholesterol Catabolism

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Thomas Q de Aguiar Vallim ◽  
Elizabeth J Tarling ◽  
Hannah Ahn ◽  
Lee R Hagey ◽  
Casey E Romanoski ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Acid Metabolism ◽  
Metabolic Diseases ◽  
Cholesterol Metabolism ◽  
Transcriptional Repressor ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Bile Acid Metabolism ◽  
Biliary Bile Acid

Elevated circulating cholesterol levels is a major risk factor for cardiovascular diseases (CVD), and therefore understanding pathways that affect cholesterol metabolism are important for potential treatment of CVD. The major route for cholesterol excretion is through its catabolism to bile acids. Specific bile acids are also potent signaling molecules that modulate metabolic pathways affecting lipid, glucose and bile acid homeostasis. Bile acids are synthesized from cholesterol in the liver, and the key enzymes involved in bile acid synthesis ( Cyp7a1 , Cyp8b1 ) are regulated transcriptionally by the nuclear receptor FXR. We have identified an FXR-regulated pathway upstream of a transcriptional repressor that controls multiple bile acid metabolism genes. We identify MafG as an FXR target gene and show that hepatic MAFG overexpression represses genes of the bile acid synthetic pathway, and modifies the biliary bile acid composition. In contrast, MafG loss-of-function studies cause de-repression of the bile acid genes with concordant changes in biliary bile acid levels. Finally, we identify functional MafG response elements in bile acid metabolism genes using ChIP-Seq analysis. Our studies identify a molecular mechanism for the complex feedback regulation of bile acid synthesis controlled by FXR. The identification of this pathway will likely have important implications in metabolic diseases.

scholarly journals Intestine-Specific Overexpression of LDLR Enhances Cholesterol Excretion and Induces Metabolic Changes in Male Mice

Endocrinology ◽  
2018 ◽  
Vol 160 (4) ◽  
pp. 744-758 ◽  
Author(s):  
Luca Meoli ◽  
Danny Ben-Zvi ◽  
Courtney Panciotti ◽  
Stephanie Kvas ◽  
Palmenia Pizarro ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Cholesterol Metabolism ◽  
Treatment Options ◽  
Density Lipoprotein ◽  
Cholesterol Absorption ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Metabolic Effects ◽  
Cholesterol Levels ◽  
Cholesterol Excretion

Abstract Roux-en-Y gastric bypass (RYGB) surgery is one of the most effective treatment options for severe obesity and related comorbidities, including hyperlipidemia, a well-established risk factor of cardiovascular diseases. Elucidating the molecular mechanisms underlying the beneficial effects of RYGB may facilitate development of equally effective, but less invasive, treatments. Recent studies have revealed that RYGB increases low-density lipoprotein receptor (LDLR) expression in the intestine of rodents. Therefore, in this study we first examined the effects of RYGB on intestinal cholesterol metabolism in human patients, and we show that they also exhibit profound changes and increased LDLR expression. We then hypothesized that the upregulation of intestinal LDLR may be sufficient to decrease circulating cholesterol levels. To this end, we generated and studied mice that overexpress human LDLR specifically in the intestine. This perturbation significantly affected intestinal metabolism, augmented fecal cholesterol excretion, and induced a reciprocal suppression of the machinery related to luminal cholesterol absorption and bile acid synthesis. Circulating cholesterol levels were significantly decreased and, remarkably, several other metabolic effects were similar to those observed in RYGB-treated rodents and patients, including improved glucose metabolism. These data highlight the importance of intestinal cholesterol metabolism for the beneficial metabolic effects of RYGB and for the treatment of hyperlipidemia.

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