scholarly journals Effect of type of dietary non‐protein energy source (starch vs. fat) on the body bile acid pool size and composition, faecal bile acid loss and bile acid synthesis in rainbow trout ( Oncorhynchus mykiss )

2021 ◽  
Author(s):  
Thomas W. O. Staessen ◽  
Marc C. J. Verdegem ◽  
Marit A. J. Nederlof ◽  
Ep H. Eding ◽  
Johan W. Schrama
F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 2029 ◽  
Author(s):  
John YL Chiang

Bile acids are derived from cholesterol to facilitate intestinal nutrient absorption and biliary secretion of cholesterol. Recent studies have identified bile acids as signaling molecules that activate nuclear farnesoid X receptor (FXR) and membrane G protein-coupled bile acid receptor-1 (Gpbar-1, also known as TGR5) to maintain metabolic homeostasis and protect liver and other tissues and cells from bile acid toxicity. Bile acid homeostasis is regulated by a complex mechanism of feedback and feedforward regulation that is not completely understood. This review will cover recent advances in bile acid signaling and emerging concepts about the classic and alternative bile acid synthesis pathway, bile acid composition and bile acid pool size, and intestinal bile acid signaling and gut microbiome in regulation of bile acid homeostasis.


2020 ◽  
Vol 61 (11) ◽  
pp. 1450-1463 ◽  
Author(s):  
Solenne Marion ◽  
Lyne Desharnais ◽  
Nicolas Studer ◽  
Yuan Dong ◽  
Matheus D. Notter ◽  
...  

Bile acids, which are synthesized from cholesterol by the liver, are chemically transformed along the intestinal tract by the gut microbiota, and the products of these transformations signal through host receptors, affecting overall host health. These transformations include bile acid deconjugation, oxidation, and 7α-dehydroxylation. An understanding of the biogeography of bile acid transformations in the gut is critical because deconjugation is a prerequisite for 7α-dehydroxylation and because most gut microorganisms harbor bile acid transformation capacity. Here, we used a coupled metabolomic and metaproteomic approach to probe in vivo activity of the gut microbial community in a gnotobiotic mouse model. Results revealed the involvement of Clostridium scindens in 7α-dehydroxylation, of the genera Muribaculum and Bacteroides in deconjugation, and of six additional organisms in oxidation (the genera Clostridium, Muribaculum, Bacteroides, Bifidobacterium, Acutalibacter, and Akkermansia). Furthermore, the bile acid profile in mice with a more complex microbiota, a dysbiosed microbiota, or no microbiota was considered. For instance, conventional mice harbor a large diversity of bile acids, but treatment with an antibiotic such as clindamycin results in the complete inhibition of 7α-dehydroxylation, underscoring the strong inhibition of organisms that are capable of carrying out this process by this compound. Finally, a comparison of the hepatic bile acid pool size as a function of microbiota revealed that a reduced microbiota affects host signaling but not necessarily bile acid synthesis. In this study, bile acid transformations were mapped to the associated active microorganisms, offering a systematic characterization of the relationship between microbiota and bile acid composition.


2003 ◽  
Vol 284 (4) ◽  
pp. G551-G557 ◽  
Author(s):  
Michael Fuchs

Bile acids, amphipathic detergent-like molecules synthesized from cholesterol, are highly conserved by means of enterohepatic circulation. They participate in the generation of bile flow and biliary lipid secretion and also promote absorption of fat-soluble vitamins and lipids. Conversion of cholesterol to bile acids represents a quantitatively important route to eliminate cholesterol from the body. Regulation of bile acid synthesis involves a complex and interrelated group of transcription regulators that link bile acid synthesis to cholesterol and fatty acid metabolism. Targeting key steps of bile acid synthetic pathways as well as the metabolic network that maintains homeostatic levels of lipids should provide exciting novel opportunities for the treatment of cardiovascular and liver diseases.


2009 ◽  
Vol 297 (1) ◽  
pp. G144-G151 ◽  
Author(s):  
Katie T. Burke ◽  
Paul S. Horn ◽  
Patrick Tso ◽  
James E. Heubi ◽  
Laura A. Woollett

Intraluminal concentrations of bile acids are low in newborn infants and increase rapidly after birth, at least partly owing to increased bile acid synthesis rates. The expansion of the bile acid pool is critical since bile acids are required to stimulate bile flow and absorb lipids, a major component of newborn diets. The purpose of the present studies was to determine the mechanism responsible for the increase in bile acid synthesis rates and the subsequent enlargement of bile acid pool sizes (BAPS) during the neonatal period, and how changes in circulating hormone levels might affect BAPS. In the hamster, pool size was low just after birth and increased modestly until 10.5 days postpartum (dpp). BAPS increased more significantly (∼3-fold) between 10.5 and 15.5 dpp. An increase in mRNA and protein levels of cholesterol 7α-hydroxylase (Cyp7a1), the rate-limiting step in classical bile acid synthesis, immediately preceded an increase in BAPS. In contrast, levels of oxysterol 7α-hydroxylase (Cyp7b1), a key enzyme in bile acid synthesis by the alternative pathway, were relatively elevated by 1.5 dpp. farnesyl X receptor (FXR) and short heterodimeric partner (SHP) mRNA levels remained relatively constant at a time when Cyp7a1 levels increased. Finally, although simultaneous increases in circulating cortisol and Cyp7a1 levels occurred, precocious expression of Cyp7a1 could not be induced in neonatal hamsters with dexamethasone. Thus the significant increase in Cyp7a1 levels in neonatal hamsters is due to mechanisms independent of the FXR and SHP pathway and cortisol.


2002 ◽  
Vol 282 (6) ◽  
pp. G926-G931 ◽  
Author(s):  
Bryan Goodwin ◽  
Steven A. Kliewer

Bile acids are required for the absorption of lipids and fat-soluble vitamins. The hepatic biosynthesis of bile acids is a major pathway for the catabolism and removal of cholesterol from the body. Because of their intrinsic toxicity, bile acid synthesis, transport, and metabolism must be tightly regulated. It is now apparent that members of the nuclear receptor family of lipid-activated transcription factors are key regulators of these physiological processes. A greater understanding of these receptors should afford novel opportunities for therapeutic intervention in chronic diseases such as cholestasis and dyslipidemia.


2018 ◽  
Vol 314 (1) ◽  
pp. R58-R70 ◽  
Author(s):  
Tengfei Zhu ◽  
Geneviève Corraze ◽  
Elisabeth Plagnes-Juan ◽  
Edwige Quillet ◽  
Mathilde Dupont-Nivet ◽  
...  

When compared with fish meal and fish oil, plant ingredients differ not only in their protein content and amino acid and fatty acid profiles but are also devoid of cholesterol, the major component of cell membrane and precursor of several bioactive compounds. Based on these nutritional characteristics, plant-based diets can affect fish physiology and cholesterol metabolism. To investigate the mechanisms underlying cholesterol homeostasis, rainbow trout were fed from 1 g body wt for 6 mo with a totally plant-based diet (V), a marine diet (M), and a marine-restricted diet (MR), with feed intake adjusted to that of the V group. The expression of genes involved in cholesterol synthesis, esterification, excretion, bile acid synthesis, and cholesterol efflux was measured in liver. Results showed that genes involved in cholesterol synthesis were upregulated in trout fed the V diet, whereas expression of genes related to bile acid synthesis ( cyp7a1) and cholesterol elimination ( abcg8) were reduced. Feeding trout the V diet also enhanced the expression of srebp-2 while reducing that of lxrα and miR-223. Overall, these data suggested that rainbow trout coped with the altered nutritional characteristics and absence of dietary cholesterol supply by increasing cholesterol synthesis and limiting cholesterol efflux through molecular mechanisms involving at least srebp-2, lxrα, and miR-223. However, plasma and body cholesterol levels in trout fed the V diet were lower than in fish fed the M diet, raising the question of the role of cholesterol in the negative effect of plant-based diet on growth.


Author(s):  
Caitlin Vonderohe ◽  
Gregory Guthrie ◽  
Barbara Stoll ◽  
Shaji Chacko ◽  
Harry Dawson ◽  
...  

Background & Aims: The tissue specific molecular mechanisms involved in perinatal liver and intestinal FXR-FGF19 signaling are poorly defined. Our aim was to establish how gestational age and feeding status affect bile acid synthesis pathway, bile acid pool size, ileal response to bile acid stimulation, genes involved in bile acid-FXR-FGF19 signaling and plasma FGF19 in neonatal pigs. Methods Term (n=23) and preterm (n=33) pigs were born via cesarean section at 100% and 90% gestation, respectively. Plasma FGF19, hepatic bile acid and oxysterol profiles, and FXR target gene expression was assessed in pigs at birth and after a bolus feed on day 3 of life. Pig ileal tissue explants were used to measure signaling response to bile acids. Results Preterm pigs had smaller, more hydrophobic bile acid pools, lower plasma FGF19, and blunted FXR-mediated ileal response to bile acid stimulation than term pigs. GATA-4 expression was higher in jejunum than ileum, and was higher in preterm than term pig ileum. Hepatic oxysterol analysis suggested dominance of the alternative pathway of bile acid synthesis in neonates, regardless of gestational age and persists in preterm pigs after feeding on day 3. Conclusion These results highlight the tissue-specific molecular basis for the immature enterohepatic bile acid signaling via FXR-FGF19 in preterm pigs and may have implications for disturbances of bile acid homeostasis and metabolism in preterm infants.


Author(s):  
Galina V. Volynets ◽  
A. I. Khavkin ◽  
T. A. Skvortsova ◽  
A. V. Nikitin ◽  
V. V. Matkash

The review presents data on the effect of the intestinal microbiota on the regulation of the synthesis and metabolism of bile acids. Violations of the bile acid pool have been shown to be accompanied by an imbalance of the intestinal microbiota, which can determine the dynamics of the formation of cholestatic liver diseases and their progression up to cirrhosis of the liver. Impaired bile acid synthesis is often caused by an imbalance in the intestinal microbiome. Changes in the complex connections of the intestinal microbiome and the metabolism of bile acids influence the formation of liver and intestinal diseases. More and more research has been noted to be devoted to the problem of the axis of the liver and intestines and its significance in the pathogenesis of various forms of the pathology of the liver and intestines.


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