Comparison of simple extraction procedures in liquid chromatography⿿mass spectrometry based determination of serum 7α-hydroxy-4-cholesten-3-one, a surrogate marker of bile acid synthesis

LeníL·ek, Martin; Vecka, Marek; Žížalová, Kateřina; Vı́tek, Libor

doi:10.1016/j.jchromb.2016.08.046

Cited by 17 publications

(10 citation statements)

References 9 publications

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“…FGF19 was assayed by sandwich enzyme‐linked immunosorbent assay as described . Levels of 7‐alpha‐hydroxy‐4‐cholesten‐3‐one (C4), a systemic marker of bile salt synthesis, were determined as described . If C4 levels were not detectable, values were set to the lower limit of detection, i.e., 0.1 ng/mL.…”

Section: Methodsmentioning

confidence: 99%

Gallbladder Dyskinesia Is Associated With an Impaired Postprandial Fibroblast Growth Factor 19 Response in Critically Ill Patients

et al. 2019

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Critical illness is associated with a disturbed regulation of gastrointestinal hormones resulting in functional and metabolic anomalies. Fibroblast growth factor 19 (FGF19) is an ileum‐derived metabolic hormone induced by bile salts upon gallbladder emptying after enteral nutrient stimulation. Our aim was to study the nutrient‐stimulated FGF19 response in 24 patients admitted to the intensive care unit (ICU) compared with 12 healthy controls. All subjects received intraduodenal high‐lipid nutrient infusion for 120 minutes. Blood was collected every 30 minutes until 1 hour after infusion, and gallbladder emptying was studied by ultrasound. Serum levels of bile salts and FGF19 were assessed. ICU patients had significantly higher fasting bile salt serum levels compared with controls, whereas FGF19 serum levels were similar. In both groups, nutrient infusion elicited substantial bile salt elevations (P < 0.001), peaking at 90 minutes, albeit with a significantly lower peak in the ICU patients (P = 0.029). In controls, FGF19 was significantly elevated relative to baseline from 120 minutes onward (P < 0.001). In ICU patients, the FGF19 response was blunted, as reflected by significantly lower FGF19 elevations at 120, 150, and 180 minutes (P < 0.05) and significantly lower area under the curve (AUC) values compared with controls (P < 0.001). Gallbladder dysmotility was associated with the impaired FGF19 response in critical illness. The gallbladder ejection fraction correlated positively with FGF19 AUC values (ρ = +0.34, P = 0.045). In 10 of 24 ICU patients, gallbladder emptying was disturbed. These patients had significantly lower FGF19 AUC values (P < 0.001). Gallbladder emptying and the FGF19 response were respectively disturbed or absent in patients receiving norepinephrine. Conclusion: The nutrient‐stimulated FGF19 response is impaired in ICU patients, which is mechanistically linked to gallbladder dysmotility in critical illness. This may contribute to disturbed liver metabolism in these patients and has potential as a nutritional biomarker.

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Section: Methodsmentioning

confidence: 99%

Gallbladder Dyskinesia Is Associated With an Impaired Postprandial Fibroblast Growth Factor 19 Response in Critically Ill Patients

et al. 2019

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“…Plasma FGF19 and FGF21 were determined using specific enzyme‐linked immunosorbent assays (ELISAs; lower detection limit of 0.01 ng/mL for both assays) as described elsewhere . Plasma C4 was measured using liquid chromatography‐mass spectrometry (LC‐MS) after acetonitrile precipitation, with a lower detection limit of 1 ng/mL. Standard diagnostic assays were used to measure levels of conjugated bilirubin, plasma transaminases, fat‐soluble vitamins, total cholesterol, albumin and coagulation factors [i.e.…”

Section: Methodsmentioning

confidence: 99%

The cholic acid extension study in Zellweger spectrum disorders: Results and implications for therapy

Klouwer

Koot

Berendse

et al. 2019

J of Inher Metab Disea

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Introduction Currently, no therapies are available for Zellweger spectrum disorders (ZSDs), a group of genetic metabolic disorders characterised by a deficiency of functional peroxisomes. In a previous study, we showed that oral cholic acid (CA) treatment can suppress bile acid synthesis in ZSD patients and, thereby, decrease plasma levels of toxic C27‐bile acid intermediates, one of the biochemical abnormalities in these patients. However, no effect on clinically relevant outcome measures could be observed after 9 months of CA treatment. It was noted that, in patients with advanced liver disease, caution is needed because of possible hepatotoxicity. Methods An extension study of the previously conducted pretest‐posttest design study was conducted including 17 patients with a ZSD. All patients received oral CA for an additional period of 12 months, encompassing a total of 21 months of treatment. Multiple clinically relevant parameters and markers for bile acid synthesis were assessed after 15 and 21 months of treatment. Results Bile acid synthesis was still suppressed after 21 months of CA treatment, accompanied with reduced levels of C27‐bile acid intermediates in plasma. These levels significantly increased again after discontinuation of CA. No significant changes were found in liver tests, liver elasticity, coagulation parameters, fat‐soluble vitamin levels or body weight. Conclusions Although CA treatment did lead to reduced levels of toxic C27‐bile acid intermediates in ZSD patients without severe liver fibrosis or cirrhosis, no improvement of clinically relevant parameters was observed after 21 months of treatment. We discuss the implications for CA therapy in ZSD based on these results.

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“…Methanolic extracts were analysed using an adaptation 38 of a previously described method for BA measurement by HPLC-MS/MS 39 on a 6420 Triple Quad LC/MS device (Agilent Technologies, Santa Clara, CA). The BA precursor C4 was determined in serum after acetonitrile precipitation/extraction 40 by a modification of an HPLC-MS/MS method 41 .…”

Section: Methodsmentioning

confidence: 99%

Lactation during cholestasis: Role of ABC proteins in bile acid traffic across the mammary gland

Blazquez

Macı́as

Cives-Losada

et al. 2017

Sci Rep

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Transporters involved in bile acid (BA) handling by the mammary gland are poorly understood. Here we have investigated the role of ABC proteins in blood-milk BA traffic and its sensitivity to maternal cholestasis. BA concentrations in rat and mouse serum were higher than in milk. BA profiles in both fluids were also different. In mammary gland, mRNA levels of ABC pumps transporting BAs were high for Bcrp, less abundant for Mrp1, Mrp3 and Mrp4 and negligible for Bsep and Mrp2. Milk BA concentrations were lower in Abcg2 −/− than in wild-type mice. Taurocholate administration (5 µmol, i.p.) increased 20-fold BA concentrations in serum, but only moderately in milk, even in Abcg2 −/− mice. Bile duct ligation (BDL) in pregnant rats markedly increased serum BA concentrations, which was not proportionally reflected in milk. In rat mammary tissue, Mrp4 was up-regulated by BDL. Serum BA levels were 2-fold higher in 10-day-old neonates of the BDL group, whereas their body weight was lower. The exchange of breastfeeding mothers immediately after birth reverted the situation without changes in endogenous BA synthesis. In conclusion, Bcrp is involved in BA secretion into milk, whereas Mrp4 participates in a blood-milk barrier that protects neonates from maternal hypercholanemia during breastfeeding.

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Comparison of simple extraction procedures in liquid chromatography⿿mass spectrometry based determination of serum 7α-hydroxy-4-cholesten-3-one, a surrogate marker of bile acid synthesis

Cited by 17 publications

References 9 publications

Gallbladder Dyskinesia Is Associated With an Impaired Postprandial Fibroblast Growth Factor 19 Response in Critically Ill Patients

Gallbladder Dyskinesia Is Associated With an Impaired Postprandial Fibroblast Growth Factor 19 Response in Critically Ill Patients

The cholic acid extension study in Zellweger spectrum disorders: Results and implications for therapy

Lactation during cholestasis: Role of ABC proteins in bile acid traffic across the mammary gland

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