Foetal ‘flat’ bile acids reappear during human liver regeneration after surgery

Stärkel, Peter; Shindano, Tony Akilimali; Horsmans, Yves; Gigot, Jean‐François; Fernandez-Tagarro, Maria; Marin, José J.G.; Monte, María J.

doi:10.1111/j.1365-2362.2008.02059.x

Cited by 11 publications

(20 citation statements)

References 22 publications

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“…It is also important to emphasize that, while powerful, the adaptive face of BA signaling may be overwhelmed if the BA overload would be too high for a remnant liver that is too small. This could be the case especially after extended PH, although only limited reports have been published [[23,24,25], and unpubl. data].…”

Section: Bas and Liver Regenerationmentioning

confidence: 99%

“…A relative decrease of CDCA and secondary BA as compared with an increase in CA was observed in the first days after PH in the rat, suggesting that the BA pool shifted toward a more hydrophilic composition early during regeneration. Also, the reappearing of more hydrophilic fetal BA (so-called ‘flat BA') during regeneration has been proposed, although the relevance for liver growth still remains speculative [23,52]. However, it was not known if the regulation of BA pool hydrophobicity would be crucial for hepatocyte protection and proliferation after PH or injury.…”

Section: Tgr5 Protects the Liver Against Ba Overload After Phmentioning

confidence: 99%

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The Bile Acid Receptor TGR5 and Liver Regeneration

Jourdainne

Péan²,

Doignon³

et al. 2015

Dig Dis

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Background: Most of the literature on the bile acid (BA) membrane receptor TGR5 is dedicated to its potential role in the metabolic syndrome, through its regulatory impact on energy expenditure, insulin and GLP-1 secretion, and inflammatory processes. While the receptor was cloned in 2002, very little data are available on TGR5 functions in the normal and diseased liver. However, TGR5 is highly expressed in Kupffer cells and liver endothelial cells, and is particularly enriched in the biliary tract [cholangiocytes and gallbladder (GB) smooth muscle cells]. We recently demonstrated that TGR5 has a crucial protective impact on the liver in case of BA overload, including after partial hepatectomy. Key Messages: TGR5-KO mice after PH exhibited periportal bile infarcts, excessive hepatic inflammation and defective adaptation of biliary composition (bicarbonate and chloride). Most importantly, TGR5-KO mice had a more hydrophobic BA pool, with more secondary BA than WT animals, suggesting that TGR5-KO bile may be harmful for the liver, mainly in situations of BA overload. As GB is both the tissue displaying the highest level of TGR5 expression and a crucial physiological site for the regulation of BA pool hydrophobicity by reducing secondary BA, we investigated whether TGR5 may control BA pool composition through an impact on GB. Preliminary data suggest that in the absence of TGR5, reduced GB filling dampens the cholecystohepatic shunt, resulting in more secondary BA, more hydrophobic BA pool and extensive liver injury in case of BA overload. Conclusions: In the setting of BA overload, TGR5 is protective of the liver through the regulation of not only secretory and inflammatory processes, but also through the control of BA pool composition, at least in part by targeting the GB. Thereby, TGR5 appears to be crucial for protecting the regenerating liver from BA overload.

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Section: Bas and Liver Regenerationmentioning

confidence: 99%

Section: Tgr5 Protects the Liver Against Ba Overload After Phmentioning

confidence: 99%

The Bile Acid Receptor TGR5 and Liver Regeneration

Jourdainne

Péan²,

Doignon³

et al. 2015

Dig Dis

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“…Thus, it follows that the flat BAs found in the rapidly proliferating hepatocytes of HCC and other hepatic cancers would also be found in the regenerating liver, and indeed, they are. In the urine of patients who had undergone partial hepatectomy (PH), flat BAs – both the Δ 4 -unsaturated and allo -BAs – were significantly increased at day 3 following surgery and continued to rise for the next seven days (the remainder of the study), reaching an increase of up to 8-fold control values (table 2) [11]. Though total urinary BA output was similar in all patients examined, excretion of flat BAs was significantly higher for some patients that had undergone major PH – meaning a larger portion of the liver was removed – versus those in the minor PH group [11].…”

Section: Recurrence In Diseasementioning

confidence: 99%

“…Most of these species are still poorly characterized [3]. One of the least studied subspecies are the “flat” BAs, a group of C 24 cholanoic acids that retain the planar structure of their cholesterol predecessor instead of the “bent” or “twisted” structure of the typical mammalian BAs [2, 4–11]. These so-called “flat” or “planar” BAs comprise several subspecies and will be the focus of this review.…”

Section: Introductionmentioning

confidence: 99%

“…What makes these molecules relevant, however, is not necessarily their importance in early life, but instead their recurrence in adult patients suffering from various types of liver injury or disease, such as cancer [4, 11]. As discussed below, these typically fetal flat BAs become abundant at various stages of hepatocellular carcinoma, following liver ablation, and in other malignancies and subsequently disappear upon recovery.…”

Section: Introductionmentioning

confidence: 99%

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Planar bile acids in health and disease

Shiffka

Kane

Swaan

2017

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Bile acids are the amphipathic primary end-products of cholesterol metabolism that aid in digestion as well as participate in signal transduction in several hepatic and enteric pathways. Despite the reputation of bile acids as signaling molecules implicated in disease states such as cancer and diabetes, there remain numerous bile acid species that are weakly characterized in either physiological or pathological conditions. This review presents one such group: the flat or planar bile acids, a set of bile acids found in humans during infancy and occurring again during certain diseases. As their name implies, these molecules are structurally distinct from the typical human bile acids, retaining the planar structure of their cholesterol predecessor instead of bending or twisting at the A ring. This review defines these species of bile acids in detail and describes their presence in infancy, gestation, and in disease. The large gaps in research regarding the flat bile acids are highlighted and all available experimental knowledge collected as far as 60 years ago is summarized. Further, the potential for these molecules as endogenous biomarkers of liver disease and injury is discussed. Finally, the flat bile salts found in humans are compared to the ancestral and evolutionary older bile salts, which similarly have a flat steroidal structure, as mechanisms of flat bile acid biosynthesis are explored.

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Analysis of bile acids in human biological samples by microcolumn separation techniques: A review

2020

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Bile acids are a group of compounds essential for lipid digestion and absorption with a steroid skeleton and a carboxylate side chain usually conjugated to glycine or taurine. Bile acids are regulatory molecules for a number of metabolic processes and can be used as biomarkers of various disorders. Since the middle of the twentieth century, the detection of bile acids has evolved from simple qualitative analysis to accurate quantification in complicated mixtures. Advanced methods are required to characterize and quantify individual bile acids in these mixtures. This article overviews the literature from the last two decades (2000-2020) and focuses on bile acid analysis in various human biological samples. The methods for sample preparation, including the sample treatment of conventional (blood plasma, blood serum, and urine) and unconventional samples (bile, saliva, duodenal/gastric juice, feces, etc.) are shortly discussed. Eventually, the focus is on novel analytical approaches and methods for each particular biological sample, providing an overview of the microcolumn separation techniques, such as high-performance liquid chromatography, gas chromatography, and capillary electrophoresis, used in their analysis. This is followed by a discussion on selected clinical applications.

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Foetal ‘flat’ bile acids reappear during human liver regeneration after surgery

Cited by 11 publications

References 22 publications

The Bile Acid Receptor TGR5 and Liver Regeneration

The Bile Acid Receptor TGR5 and Liver Regeneration

Planar bile acids in health and disease

Analysis of bile acids in human biological samples by microcolumn separation techniques: A review

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