Diurnal rhythms of bile acid production in the rat

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.

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Liver denervation does not alter the circadian rhythm of bile acid synthesis in rats

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1991.261.5.g799 ◽

1991 ◽

Vol 261 (5) ◽

pp. G799-G802 ◽

Cited By ~ 1

Author(s):

M. L. Gilberstadt ◽

L. L. Bellinger ◽

S. Lindblad ◽

W. C. Duane

Keyword(s):

Circadian Rhythm ◽

Bile Acid ◽

Feedback Regulation ◽

Acid Synthesis ◽

Bile Acid Synthesis ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Significant Difference ◽

Free Running ◽

Hepatic Nerves

In both rats and humans there is a distinct circadian rhythm of bile acid synthesis that is independent of feedback regulation. To determine whether the circadian rhythm is directly mediated via hepatic nerves, bile acid synthesis was studied in selectively liver-denervated male Sprague-Dawley rats in a bile fistula model. Complete denervation was confirmed by histofluorescent staining for neural elements in frozen sections of livers. There was no significant difference in mean bile acid synthesis, amplitude of the circadian rhythm, or time of peak synthesis between the denervated rats and nondenervated controls. In one denervated rat studied four times at weekly intervals, there was no shift in acrophase, indicating that the rhythm had not become free running. We conclude that signals arriving via hepatic nerves neither directly cause nor entrain the circadian rhythm of bile acid synthesis in rats.

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

Nutrients ◽

10.3390/nu11071439 ◽

2019 ◽

Vol 11 (7) ◽

pp. 1439 ◽

Cited By ~ 2

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.

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

Journal of Biological Chemistry ◽

10.1074/jbc.m113.485987 ◽

2013 ◽

Vol 288 (52) ◽

pp. 37154-37165 ◽

Cited By ~ 38

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

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Biliary Excretion of Chylomicron Remnant Cholesterol in the Rat: Responses to the Expansion of Their Plasma Pool and Promoting Role of Stimulated Bile-Acid Synthesis

Clinical Science ◽

10.1042/cs0890121 ◽

1995 ◽

Vol 89 (2) ◽

pp. 121-128 ◽

Cited By ~ 2

Author(s):

Massimino Carrella ◽

Annalisa Csillaghy ◽

Renato de Mercato ◽

Agesilao D'Arienzo

Keyword(s):

Bile Acid ◽

Bile Acids ◽

Total Sterol ◽

Acid Synthesis ◽

Bile Acid Synthesis ◽

Time Interval ◽

Neutral Sterol ◽

Biliary Lipids ◽

Bile Fistula ◽

Remnant Cholesterol

1. Chylomicron remnants, the intermediate intestinal lipoproteins carrying the bulk of dietary cholesterol, are actively taken up and degraded in the hepatocytes, releasing cholesterol which can be excreted in bile. To study this pathway, a mass of remnants, leading to a consistent rise in hepatic cholesterol, was administered as an intravenous bolus in rats with chronic bile fistula equilibrated by water, electrolyte and taurocholate infusions, and changes in biliary lipids and bile acids were evaluated for up to 24 h in comparison with baseline. 2. A mean 16% increase in the net output of bile acids was observed at each time interval after lipoprotein injection, accounting for a 24 h cumulative excretion of approximately one-third of the administered cholesterol mass. These changes did not reach statistical significance however. The cholesterol output and concentrations of all biliary lipids did not vary either. Without taurocholate replacement, remnants injection was followed by a 15–20% decrease in bile acid and bile lipid secretion, presumably due to an insufficient hepatic bile-acid flux. 3. When [3H]cholesterol-labelled remnants were administered at the same mass in the chronic equilibrated bile fistula model, 21% of injected radioactivity was excreted in 24 h, distributing mostly in acidic rather than neutral sterols (20.02 ± 1.85 compared with 1.07 ± 0.04), with an acidic to neutral sterol mean ratio of 16. 4. To exclude interfering effects from the administered cholesterol mass and chronic bile fistula, 3H-labelled remnants were also studied as a cholesterol trace injected in rats with acute bile fistula. In this case, however, 24 h total sterol radioactivity only reached approximately 10% of that injected, and partitioned relatively less in acidic (6.84 ± 0.59) than in neutral (3.15 ± 0.39) sterols, with an acidic to neutral sterol mean ratio of 2. 5. The study suggests that remnant cholesterol reaches bile mainly in the form of bile acids, by a steady slow-rate process which is magnified under conditions of stimulated bile-acid synthesis.

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