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.

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 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 (7&alpha;-hydroxy-cholesterol, 27-hydroxy-cholesterol) corrected for cholesterol concentration (R_sterols). Over 12 weeks, 116 obese subjects (BMI 31.7, range 28.1 &ndash; 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 &plusmn; 18.18 mg/dl, 5.6%) than under placebo treatment (-1.00 &plusmn; 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 &ndash; 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 &plusmn; 18.18 mg/dl, 5.6%) than under placebo treatment (-1.00 &plusmn; 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_7&alpha;-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 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 Metabolism of sulfonate analogs of ursodeoxycholic acid and their effects on biliary bile acid composition in hamsters.

1993 ◽  
Vol 34 (3) ◽  
pp. 429-435
Author(s):  
T Mikami ◽  
K Kihira ◽  
S Ikawa ◽  
M Yoshii ◽  
S Miki ◽  
...  
Keyword(s):  
Bile Acid ◽  
Ursodeoxycholic Acid ◽  
Acid Composition ◽  
Biliary Bile Acid

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.

Abstract 131: Restoration of ER Stress and Induction of FGF15/19 Independently Rescue ABCG5 ABCG8 Sterol Transporter

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Yuhuan Wang ◽  
Kai Su ◽  
Nadezhda Sabeva ◽  
Ailing Ji ◽  
Deneys van der Westhuyzen ◽  
...  
Keyword(s):  
Bile Acid ◽  
Er Stress ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Biliary Cholesterol ◽  
Leptin Receptors ◽  
Insulin Resistant ◽  
Protein Levels ◽  
The Face ◽  
Biliary Cholesterol Secretion

Mice lacking leptin (ob/ob) or its receptor (db/db) are obese, insulin resistant and have reduced levels of biliary cholesterol due, in part, to reduced levels of hepatic ABCG5 ABCG8 (G5G8). Chronic leptin replacement restores G5G8 abundance and increases biliary cholesterol concentrations, but the molecular mechanism responsible for G5G8 regulation remains unclear. In the current study, we conducted a series of experiments to address potential mechanisms. To determine if leptin signaling directly regulates hepatic G5G8 abundance, we acutely replaced leptin in ob/ob mice and deleted hepatic leptin receptors in lean mice. Neither manipulation altered G5G8 abundance or biliary cholesterol. Similarly, hepatic vagotomy had no effect on G5G8. Alternatively, the G5G8 protein complex may be decreased due to compromised ER stress. It has been previously reported that tauroursodeoxycholate (TUDCA) alleviates ER stress. It also increases G5G8 and biliary cholesterol in both lean and db/db mice. The ER chaperone protein, glucose regulated protein 78-kDa (GRP78) can restore ER function and reduce unfolded protein response (UPR) signaling. Therefore, we tested the hypothesis that expression of GRP78 could rescue G5G8 in db/db mice. Adenovirus encoding GRP78 was administered to db/db mice and the effect on hepatic G5G8 was determined. G5 and G8 proteins and biliary cholesterol were increased in the absence of changes in mRNAs encoding either protein. However, TUDCA has also been shown to induce FGF15. In several models of bile acid feeding, FGF15/19 is stimulated in ileum and activates its receptor in liver to repress bile acid synthesis. Simultaneously, G5G8 and biliary cholesterol secretion are elevated. To determine if FGF15/19 had a direct effect on hepatic G5G8, we injected C57BL/6 mice with recombinant FGF19. CYP7A1 and CYP8B1 mRNA expression were both strongly suppressed, whereas G5G8 increased at both mRNA and protein levels. In conclusion, G5G8 can be rescued in ob/ob and db/db mice through multiple mechanisms that include restoration of ER functions and FGF15/19 signaling. Counter regulation of CYP7A1, CYP8B1, and G5G8 by FGF15/19 allows for the maintenance of hepatic sterol elimination in the face of expanded bile acid pool.

scholarly journals The effect of ursodeoxycholic acid on biliary bile acid composition in patients with cholesterol gallstone.

1982 ◽  
Vol 136 (3) ◽  
pp. 235-249 ◽  
Author(s):  
YOSHIHIKO KANAZAWA ◽  
MASARU KOIZUMI ◽  
HIDETOSHI HIRAKAWA ◽  
KATSUHIRO ENDO ◽  
SHIN YOSHIDA ◽  
...  
Keyword(s):  
Bile Acid ◽  
Ursodeoxycholic Acid ◽  
Acid Composition ◽  
Cholesterol Gallstone ◽  
Biliary Bile Acid

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.

Sign in / Sign up

Export Citation Format

Share Document