scholarly journals Diurnal Variation of Markers for Cholesterol Synthesis, Cholesterol Absorption, and Bile Acid Synthesis: A Systematic Review and the Bispebjerg Study of Diurnal Variations

Nutrients ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1439 ◽  
Author(s):  
Schroor ◽  
Sennels ◽  
Fahrenkrug ◽  
Jørgensen ◽  
Plat ◽  
...  
Keyword(s):  
Bile Acid ◽  
Diurnal Rhythm ◽  
Cholesterol Synthesis ◽  
Cholesterol Absorption ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Cholesterol Homeostasis ◽  
Diurnal Rhythms ◽  
Serum Samples ◽  
Targeted Interventions

Human studies have shown diurnal rhythms of cholesterol and bile acid synthesis, but a better understanding of the role of the circadian system in cholesterol homeostasis is needed for the development of targeted interventions to improve metabolic health. Therefore, we performed a systematic literature search on the diurnal rhythms of cholesterol synthesis and absorption markers and of bile acid synthesis markers. We also examined the diurnal rhythms of the cholesterol synthesis markers lathosterol and desmosterol, and of the cholesterol absorption markers cholestanol, campesterol, and sitosterol in serum samples from the Bispebjerg study. These samples were collected every three hours over a 24-hour period in healthy males (n = 24) who consumed low-fat meals. The systematic search identified sixteen papers that had examined the diurnal rhythms of the cholesterol synthesis markers lathosterol (n = 3), mevalonate (n = 9), squalene (n = 2), or the bile acid synthesis marker 7α-hydroxy-4-cholesten-3-one (C4) (n = 4). Results showed that lathosterol, mevalonate, and squalene had a diurnal rhythm with nocturnal peaks, while C4 had a diurnal rhythm with daytime peaks. Furthermore, cosinor analyses of the serum samples showed a significant diurnal rhythm for lathosterol (cosinor p < 0.001), but not for desmosterol, campesterol, sitosterol, and cholestanol (cosinor p > 0.05). In conclusion, cholesterol synthesis and bile acid synthesis have a diurnal rhythm, though no evidence for a diurnal rhythm of cholesterol absorption was found under highly standardised conditions. More work is needed to further explore the influence of external factors on the diurnal rhythms regulating cholesterol homeostasis.

scholarly journals Barleyβ-glucan reduces blood cholesterol levels via interrupting bile acid metabolism

2017 ◽  
Vol 118 (10) ◽  
pp. 822-829 ◽  
Author(s):  
Yanan Wang ◽  
Scott V. Harding ◽  
Sijo J. Thandapilly ◽  
Susan M. Tosh ◽  
Peter J. H. Jones ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Bile Acid ◽  
Cholesterol Synthesis ◽  
Cholesterol Absorption ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Cholesterol Lowering ◽  
Lowering Effect ◽  
Underlying Mechanisms ◽  
Cholesterol Lowering Effect

AbstractUnderlying mechanisms responsible for the cholesterol-lowering effect ofβ-glucan have been proposed, yet have not been fully demonstrated. The primary aim of this study was to determine whether the consumption of barleyβ-glucan lowers cholesterol by affecting the cholesterol absorption, cholesterol synthesis or bile acid synthesis. In addition, this study was aimed to assess whether the underlying mechanisms are related to cholesterol 7αhydroxylase (CYP7A1) SNP rs3808607 as proposed by us earlier. In a controlled, randomised, cross-over study, participants with mild hypercholesterolaemia (n30) were randomly assigned to receive breakfast containing 3 g high-molecular weight (HMW), 5 g low-molecular weight (LMW), 3 g LMW barleyβ-glucan or a control diet, each for 5 weeks. Cholesterol absorption was determined by assessing the enrichment of circulating13C-cholesterol over 96 h following oral administration; fractional rate of synthesis for cholesterol was assessed by measuring the incorporation rate of2H derived from deuterium oxide within the body water pool into the erythrocyte cholesterol pool over 24 h; bile acid synthesis was determined by measuring serum 7α-hydroxy-4-cholesten-3-one concentrations. Consumption of 3 g HMWβ-glucan decreased total cholesterol (TC) levels (P=0·029), but did not affect cholesterol absorption (P=0·25) or cholesterol synthesis (P=0·14). Increased bile acid synthesis after consumption of 3 g HMWβ-glucan was observed in all participants (P=0·049), and more pronounced in individuals carrying homozygous G of rs3808607 (P=0·033). In addition, a linear relationship between log (viscosity) ofβ-glucan and serum 7α-HC concentration was observed in homozygous G allele carriers. Results indicate that increased bile acid synthesis rather than inhibition of cholesterol absorption or synthesis may be responsible for the cholesterol-lowering effect of barleyβ-glucan. The pronounced TC reduction in G allele carriers of rs3808607 observed in the previous study may be due to enhanced bile acid synthesis in response to high-viscosityβ-glucan consumption in those individuals.

Diurnal rhythms of bile acid production in the rat

1979 ◽  
Vol 236 (3) ◽  
pp. R175-R179 ◽  
Author(s):  
W. C. Duane ◽  
M. L. Gilberstadt ◽  
D. M. Wiegand
Keyword(s):  
Bile Acid ◽  
Diurnal Rhythm ◽  
Dark Period ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Diurnal Rhythms ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Bile Fistula ◽  
Free Running

Diurnal rhythms of bile acid synthesis were studied in Sprague-Dawley rats maintained in 12 h of illumination and 12 h of darkness each day. Synthesis, measured as output from a chronic bile fistula, underwent a consistent diurnal change with an amplitude of about 20% around mean daily synthesis and a peak in the dark period. The peak in cholate synthesis preceded the peak in chenodeoxycholate synthesis which preceded the peak in alpha-muricholate synthesis which preceded the peak in beta-muricholate synthesis. Fasting, intravenous infusion of dexamethasone (100 microgram/kg . h), adrenalectomy, and ocular enucleation all failed to abolish the diurnal rhythm in synthesis. In one rat studied 30 days after ocular enucleation the diurnal rhythm in synthesis persisted; however, relative to 4 days after enucleation the phase of the rhythm shifted about 90 degrees suggesting that light deprivation caused the rhythm to become free-running with a period slightly different from 24 h.

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.

scholarly journals Effect of ursodeoxycholate and its taurine conjugate on bile acid synthesis and cholesterol absorption

1984 ◽  
Vol 87 (1) ◽  
pp. 130-135 ◽  
Author(s):  
William G.M. Hardison ◽  
Scott M. Grundy
Keyword(s):  
Bile Acid ◽  
Cholesterol Absorption ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Taurine Conjugate

Cholesterol Absorption and Cholesterol and Bile Acid Synthesis in Two Brothers With IDDM and Diarrhea

Diabetes Care ◽  
1994 ◽  
Vol 17 (11) ◽  
pp. 1345-1347 ◽  
Author(s):  
H. Gylling ◽  
T. A. Miettinen
Keyword(s):  
Bile Acid ◽  
Cholesterol Absorption ◽  
Acid Synthesis ◽  
Bile Acid Synthesis

scholarly journals The influence of biological sex and sex hormones on bile acid synthesis and cholesterol homeostasis

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Taylor Phelps ◽  
Erin Snyder ◽  
Erin Rodriguez ◽  
Hailey Child ◽  
Pamela Harvey
Keyword(s):  
Bile Acid ◽  
Therapeutic Potential ◽  
Cholesterol Biosynthesis ◽  
Elevated Serum ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Cholesterol Homeostasis ◽  
Cholesterol Lowering ◽  
Promising Alternative ◽  
Biological Sex

AbstractObesity and elevated serum lipids are associated with a threefold increase in the risk of developing atherosclerosis, a condition that underlies stroke, myocardial infarction, and sudden cardiac death. Strategies that aim to reduce serum cholesterol through modulation of liver enzymes have been successful in decreasing the risk of developing atherosclerosis and reducing mortality. Statins, which inhibit cholesterol biosynthesis in the liver, are considered among the most successful compounds developed for the treatment of cardiovascular disease. However, recent debate surrounding their effectiveness and safety prompts consideration of alternative cholesterol-lowering therapies, including increasing cholesterol catabolism through bile acid (BA) synthesis. Targeting the enzymes that convert cholesterol to BAs represents a promising alternative to other cholesterol-lowering approaches that treat atherosclerosis as well as fatty liver diseases and diabetes mellitus. Compounds that modify the activity of these pathways have been developed; however, there remains a lack of consideration of biological sex. This is necessary in light of strong evidence for sexual dimorphisms not only in the incidence and progression of the diseases they influence but also in the expression and activity of the proteins affected and in the manner in which men and women respond to drugs that modify lipid handling in the liver. A thorough understanding of the enzymes involved in cholesterol catabolism and modulation by biological sex is necessary to maximize their therapeutic potential.

scholarly journals Retinoic Acid-related Orphan Receptor α Regulates Diurnal Rhythm and Fasting Induction of Sterol 12α-Hydroxylase in Bile Acid Synthesis

2013 ◽  
Vol 288 (52) ◽  
pp. 37154-37165 ◽  
Author(s):  
Preeti Pathak ◽  
Tiangang Li ◽  
John Y. L. Chiang
Keyword(s):  
Retinoic Acid ◽  
Bile Acid ◽  
Diurnal Rhythm ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Orphan Receptor

scholarly journals Human liver cholesteryl ester hydrolase: cloning, molecular characterization, and role in cellular cholesterol homeostasis

2005 ◽  
Vol 23 (3) ◽  
pp. 304-310 ◽  
Author(s):  
Bin Zhao ◽  
Ramesh Natarajan ◽  
Shobha Ghosh
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Human Liver ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Human Hepatocytes ◽  
Cholesterol Homeostasis ◽  
Cholesteryl Esters ◽  
Ester Hydrolase ◽  
Hydrolysis Of

The liver regulates cholesterol homeostasis and eliminates excess cholesterol as bile acids or biliary cholesterol. Free cholesterol for bile acid synthesis or biliary secretion is obtained by the hydrolysis of stored cholesteryl esters or from cholesteryl esters taken up by the liver from high-density lipoproteins via a selective uptake pathway. The present study was undertaken to characterize the enzyme catalyzing this reaction, namely, cholesterol ester hydrolase (CEH) from the human liver, and demonstrate its role in regulating bile acid synthesis. Two cDNAs were isolated from the human liver that differed only in the presence of an additional alanine at position 18 in one of the clones. Transient transfection of COS-7 cells with a eukaryotic expression vector containing either of these two cDNAs resulted in significant increase in the hydrolysis of cholesteryl esters, authenticating these clones as human liver CEH. CEH mRNA and protein expression in human hepatocytes were demonstrated by real-time PCR and Western blot analyses, respectively, confirming the location of this enzyme in the cell type involved in hepatic cholesterol homeostasis. Overexpression of these CEH clones in human hepatocytes resulted in significant increase in bile acid synthesis, demonstrating a role for liver CEH in modulating bile acid synthesis. This CEH gene mapped on human chromosome 16, and the two clones represent two different transcript variants resulting from splice shifts at exon 1. In conclusion, these data identify that human liver CEH was expressed in hepatocytes, where it potentially regulates the synthesis of bile acids and thus the removal of cholesterol from the body.

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