Bile Acid Synthesis in Humans Has a Rapid Diurnal Variation That Is Asynchronous With Cholesterol Synthesis

Gälman, Cecilia; Angelin, Bo; Rudling, Mats

doi:10.1053/j.gastro.2005.09.009

Cited by 193 publications

(188 citation statements)

References 37 publications

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“…We found large variations in fasting BA concentrations both within and between individuals, as depicted in Figure 1. This is in line with studies of non-bariatric subjects, which found large diurnal variations within individuals [41,42] and large variations in production and concentrations between individuals [43,44].…”

Section: Discussionsupporting

confidence: 91%

Bile acid profiles over 5 years after gastric bypass and duodenal switch: results from a randomized clinical trial

Risstad

Kristinsson

Fagerland

et al. 2017

Surgery for Obesity and Related Diseases

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(2017). Bile acid profiles over 5 years following gastric bypass and duodenal switch -Results from a randomized clinical trial. Surgery for obesity and related diseases. https://doi.org/10.1016/j.soard.2017.05.024Citing this paper Please note that where the full-text provided on King's Research Portal is the Author Accepted Manuscript or Post-Print version this may differ from the final Published version. If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections. General rightsCopyright and moral rights for the publications made accessible in the Research Portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognize and abide by the legal requirements associated with these rights.•Users may download and print one copy of any publication from the Research Portal for the purpose of private study or research.•You may not further distribute the material or use it for any profit-making activity or commercial gain •You may freely distribute the URL identifying the publication in the Research Portal Take down policy If you believe that this document breaches copyright please contact librarypure@kcl.ac.uk providing details, and we will remove access to the work immediately and investigate your claim. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Section: Discussionsupporting

confidence: 91%

Bile acid profiles over 5 years after gastric bypass and duodenal switch: results from a randomized clinical trial

Risstad

Kristinsson

Fagerland

et al. 2017

Surgery for Obesity and Related Diseases

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“…The two clinically desired results were a lowering of serum LDL cholesterol levels, and based on measurements of established bio-markers for bile-acid and cholesterol synthesis (18,19), an increase in bile acid synthesis in the absence of an effect on cholesterol synthesis. In the 2-week study, KB2115 lowered serum cholesterol levels to a maximal level of 40% reduction.…”

Section: Discussionmentioning

confidence: 99%

“…Effects of KB2115 on the hypothalamic-pituitary axis were determined by measuring TSH, free and total T 3, and free and total T4. This measurement was done in the single-dose study before and at 1,6,12,18,24,30,36,48,72,96, and 120 h after administration of KB211 and in the multiple-dose study at 1, 6, 12, 18, and 24 h after the first and last dose of KB2115. An indirect RIA assay was used to estimate levels of total and free T 4 and total and free T3.…”

Section: Methodsmentioning

confidence: 99%

“…Serum lipids including cholesterol (total, LDL, HDL), triglycerides, free fatty acids, apoA-I, apoB, and lipoprotein a were measured in fasting samples. Also changes in bile acid and cholesterol synthesis rates were assessed by measurements of C4/ cholesterol and lathosterol/cholesterol as described (18,19).…”

Section: Methodsmentioning

confidence: 99%

“…For this purpose, serum levels of lathosterol were determined as a marker for total body cholesterol synthesis (18) and of 7␣-hydroxy-4-cholesten-3-one (C4) as a marker for hepatic bile acid synthesis (18,19). As shown in Fig.…”

Section: Pharmacodynamic Effects On Thyroid Hormone Homeostasis and Lmentioning

confidence: 99%

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The thyroid hormone mimetic compound KB2115 lowers plasma LDL cholesterol and stimulates bile acid synthesis without cardiac effects in humans

Berkenstam

Kristensen

Mellström

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

173

131

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Atherosclerotic cardiovascular disease is a major problem despite the availability of drugs that influence major risk factors. New treatments are needed, and there is growing interest in therapies that may have multiple actions. Thyroid hormone modulates several cardiovascular risk factors and delays atherosclerosis progression in humans. However, use of thyroid hormone is limited by side effects, especially in the heart. To overcome this limitation, pharmacologically selective thyromimetics that mimic metabolic effects of thyroid hormone and bypass side effects are under development. In animal models, such thyromimetics have been shown to stimulate cholesterol elimination through LDL and HDL pathways and decrease body weight without eliciting side effects. We report here studies on a selective thyromimetic [KB2115; (3-[[3,5-dibromo-4-[4-hydroxy-3-(1-methylethyl)-phenoxy]-phenyl]-amino]-3-oxopropanoic acid)] in hu-mans. In moderately overweight and hypercholesterolemic subjects KB2115 was found to be safe and well tolerated and elicited up to a 40% lowering of total and LDL cholesterol after 14 days of treatment. Bile acid synthesis was stimulated without evidence of increased cholesterol production, indicating that KB2115 induced net cholesterol excretion. KB2115 did not provoke detectable effects on the heart, suggesting that the pharmacological selectivity observed in animal models translates to humans. Thus, selective thyromimetics deserve further study as agents to treat dyslipidemia and other risk factors for atherosclerosis.

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Chronotherapy versus conventional statins therapy for the treatment of hyperlipidaemia

Fernandez-Tabera¹,

López‐Alcalde²,

Álvarez³

et al. 2011

Cochrane Database of Systematic Reviews

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Bile Acid Synthesis in Humans Has a Rapid Diurnal Variation That Is Asynchronous With Cholesterol Synthesis

Cited by 193 publications

References 37 publications

Bile acid profiles over 5 years after gastric bypass and duodenal switch: results from a randomized clinical trial

Bile acid profiles over 5 years after gastric bypass and duodenal switch: results from a randomized clinical trial

The thyroid hormone mimetic compound KB2115 lowers plasma LDL cholesterol and stimulates bile acid synthesis without cardiac effects in humans

Chronotherapy versus conventional statins therapy for the treatment of hyperlipidaemia

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