scholarly journals Farnesoid X receptor and bile acids regulate vitamin A storage

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ali Saeed ◽  
Jing Yang ◽  
Janette Heegsma ◽  
Albert K. Groen ◽  
Saskia W. C. van Mil ◽  
...  
Keyword(s):  
Vitamin A ◽  
Bile Acids ◽  
Mouse Liver ◽  
Retinyl Palmitate ◽  
Farnesoid X Receptor ◽  
Immune Control ◽  
Obeticholic Acid ◽  
Vitamin A Metabolism ◽  
Protein Levels ◽  
And Storage

AbstractThe nuclear receptor Farnesoid X Receptor (FXR) is activated by bile acids and controls multiple metabolic processes, including bile acid, lipid, carbohydrate, amino acid and energy metabolism. Vitamin A is needed for proper metabolic and immune control and requires bile acids for efficient intestinal absorption and storage in the liver. Here, we analyzed whether FXR regulates vitamin A metabolism. Compared to control animals, FXR-null mice showed strongly reduced (>90%) hepatic levels of retinol and retinyl palmitate and a significant reduction in lecithin retinol acyltransferase (LRAT), the enzyme responsible for hepatic vitamin A storage. Hepatic reintroduction of FXR in FXR-null mice induced vitamin A storage in the liver. Hepatic vitamin A levels were normal in intestine-specific FXR-null mice. Obeticholic acid (OCA, 3 weeks) treatment rapidly reduced (>60%) hepatic retinyl palmitate levels in mice, concurrent with strongly increased retinol levels (>5-fold). Similar, but milder effects were observed in cholic acid (12 weeks)-treated mice. OCA did not change hepatic LRAT protein levels, but strongly reduced all enzymes involved in hepatic retinyl ester hydrolysis, involving mostly post-transcriptional mechanisms. In conclusion, vitamin A metabolism in the mouse liver heavily depends on the FXR and FXR-targeted therapies may be prone to cause vitamin A-related pathologies.

scholarly journals Potential of therapeutic bile acids in the treatment of neonatal Hyperbilirubinemia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lori W. E. van der Schoor ◽  
Henkjan J. Verkade ◽  
Anna Bertolini ◽  
Sanne de Wit ◽  
Elvira Mennillo ◽  
...  
Keyword(s):  
Bile Acids ◽  
Treatment Options ◽  
Preventive Treatment ◽  
Neonatal Hyperbilirubinemia ◽  
Farnesoid X Receptor ◽  
Neurological Damage ◽  
Obeticholic Acid ◽  
Protein Levels ◽  
Gunn Rats ◽  
Plasma Bilirubin

AbstractNeonatal hyperbilirubinemia or jaundice is associated with kernicterus, resulting in permanent neurological damage or even death. Conventional phototherapy does not prevent hyperbilirubinemia or eliminate the need for exchange transfusion. Here we investigated the potential of therapeutic bile acids ursodeoxycholic acid (UDCA) and obeticholic acid (OCA, 6-α-ethyl-CDCA), a farnesoid-X-receptor (FXR) agonist, as preventive treatment options for neonatal hyperbilirubinemia using the hUGT1*1 humanized mice and Ugt1a-deficient Gunn rats. Treatment of hUGT1*1 mice with UDCA or OCA at postnatal days 10–14 effectively decreased bilirubin in plasma (by 82% and 62%) and brain (by 72% and 69%), respectively. Mechanistically, our findings indicate that these effects are mediated through induction of protein levels of hUGT1A1 in the intestine, but not in liver. We further demonstrate that in Ugt1a-deficient Gunn rats, UDCA but not OCA significantly decreases plasma bilirubin, indicating that at least some of the hypobilirubinemic effects of UDCA are independent of UGT1A1. Finally, using the synthetic, non-bile acid, FXR-agonist GW4064, we show that some of these effects are mediated through direct or indirect activation of FXR. Together, our study shows that therapeutic bile acids UDCA and OCA effectively reduce both plasma and brain bilirubin, highlighting their potential in the treatment of neonatal hyperbilirubinemia.

scholarly journals FXR activation by obeticholic acid or nonsteroidal agonists induces a human-like lipoprotein cholesterol change in mice with humanized chimeric liver

2018 ◽  
Vol 59 (6) ◽  
pp. 982-993 ◽  
Author(s):  
Romeo Papazyan ◽  
Xueqing Liu ◽  
Jingwen Liu ◽  
Bin Dong ◽  
Emily M. Plummer ◽  
...  
Keyword(s):  
Target Gene ◽  
Ldl Cholesterol ◽  
Ldl Receptor ◽  
Hdl Cholesterol ◽  
Farnesoid X Receptor ◽  
Receptor Protein ◽  
Chimeric Mice ◽  
Obeticholic Acid ◽  
Protein Levels ◽  
Mechanistic Basis

Obeticholic acid (OCA) is a selective farnesoid X receptor (FXR) agonist that regulates bile acid and lipid metabolism. FXR activation induces distinct changes in circulating cholesterol among animal models and humans. The mechanistic basis of these effects has been elusive because of difficulties in studying lipoprotein homeostasis in mice, which predominantly package circulating cholesterol in HDLs. Here, we tested the effects of OCA in chimeric mice whose livers are mostly composed (≥80%) of human hepatocytes. Chimeric mice exhibited a human-like ratio of serum LDL cholesterol (LDL-C) to HDL cholesterol (HDL-C) at baseline. OCA treatment in chimeric mice increased circulating LDL-C and decreased circulating HDL-C levels, demonstrating that these mice closely model the cholesterol effects of FXR activation in humans. Mechanistically, OCA treatment increased hepatic cholesterol in chimeric mice but not in control mice. This increase correlated with decreased SREBP-2 activity and target gene expression, including a significant reduction in LDL receptor protein. Cotreatment with atorvastatin reduced total cholesterol, rescued LDL receptor protein levels, and normalized serum LDL-C. Treatment with two clinically relevant nonsteroidal FXR agonists elicited similar lipoprotein and hepatic changes in chimeric mice, suggesting that the increase in circulating LDL-C is a class effect of FXR activation.

scholarly journals Retinol and Retinyl Palmitate in Foetal Lung Mice: Sexual Dimorphism

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Olga Carvalho ◽  
Carlos Gonçalves
Keyword(s):  
Sexual Dimorphism ◽  
Vitamin A ◽  
Hplc Analysis ◽  
Prenatal Development ◽  
Retinyl Palmitate ◽  
Control Group ◽  
Male And Female ◽  
Vitamin A Metabolism ◽  
Pregnant Females ◽  
Foetal Lung

In this work, we evaluate the lung retinoids content to study the possible difference between male and female mice during prenatal development and to comprehend if the vitamin A metabolism is similar in both genders. The study occurred between developmental days E15 and E19, and the retinol and retinyl palmitate lung contents were determined by HPLC analysis. We established two main groups: the control, consisting of foetuses obtained from pregnant females without any manipulation, and vitamin A, composed of foetuses from pregnant females submitted to vitamin A administration on developmental day E14. Each of these groups was subdivided by gender, establishing the four final groups. In the lung of control group, retinol was undetected in both genders and retinyl palmitate levels exhibited a sexual dimorphism. In the vitamin A group, we detected retinol and retinyl palmitate in both genders, and we observed a more evident sexual dimorphism for both retinoids. Our study also indicates that, from developmental day E15 to E19, there is an increase in the retinoids content in foetal lung and a gender difference in the retinoids metabolism. In conclusion, there is a sexual dimorphism in the lung retinoids content and in its metabolism during mice development.

Effect of supplemental β-carotene compared to retinyl palmitate on fatty acid profile and expression of mRNA from genes involved in vitamin A metabolism in beef feedlot cattle

2017 ◽  
Vol 88 (9) ◽  
pp. 1380-1387 ◽  
Author(s):  
Kaitlin N. Condron ◽  
Jolena N. Waddell ◽  
Matt C. Claeys ◽  
Ronald P. Lemenager ◽  
Jon P. Schoonmaker
Keyword(s):  
Fatty Acid ◽  
Vitamin A ◽  
Fatty Acid Profile ◽  
Retinyl Palmitate ◽  
Feedlot Cattle ◽  
Vitamin A Metabolism ◽  
Β Carotene

Vitamin A metabolism: α-Tocopherol modulates tissue retinol levels in vivo, and retinyl palmitate hydrolysis in vitro

1984 ◽  
Vol 230 (1) ◽  
pp. 194-202 ◽  
Author(s):  
Joseph L. Napoli ◽  
Anne M. McCormick ◽  
Brian O'Meara ◽  
Edward A. Dratz
Keyword(s):  
Vitamin A ◽  
Retinyl Palmitate ◽  
Vitamin A Metabolism

Vitamin A metabolism: new perspectives on absorption, transport, and storage

1991 ◽  
Vol 71 (4) ◽  
pp. 951-990 ◽  
Author(s):  
R. Blomhoff ◽  
M. H. Green ◽  
J. B. Green ◽  
T. Berg ◽  
K. R. Norum
Keyword(s):  
Vitamin A ◽  
Vitamin A Metabolism ◽  
And Storage

Vitamin A Metabolism in Infection

1955 ◽  
Vol 57 (2) ◽  
pp. 277-286 ◽  
Author(s):  
B. M. Kagan ◽  
Elizabeth Kaiser
Keyword(s):  
Vitamin A ◽  
Vitamin A Metabolism

Egg white peptide-based immunotherapy enhances vitamin A metabolism and induces RORγt+ regulatory T cells

2019 ◽  
Vol 52 ◽  
pp. 204-211 ◽  
Author(s):  
Daniel Lozano-Ojalvo ◽  
Mónica Martínez-Blanco ◽  
Leticia Pérez-Rodríguez ◽  
Elena Molina ◽  
Carmen Peláez ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Vitamin A ◽  
Egg White ◽  
Vitamin A Metabolism

scholarly journals Role of Bile Acids in the Regulation of Food Intake, and Their Dysregulation in Metabolic Disease

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1104
Author(s):  
Cong Xie ◽  
Weikun Huang ◽  
Richard L. Young ◽  
Karen L. Jones ◽  
Michael Horowitz ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Peptide Yy ◽  
Glycogen Synthesis ◽  
Hormone Secretion ◽  
Gastrointestinal Hormones ◽  
Farnesoid X Receptor ◽  
Gastrointestinal Hormone ◽  
Bile Acid Sequestrants

Bile acids are cholesterol-derived metabolites with a well-established role in the digestion and absorption of dietary fat. More recently, the discovery of bile acids as natural ligands for the nuclear farnesoid X receptor (FXR) and membrane Takeda G-protein-coupled receptor 5 (TGR5), and the recognition of the effects of FXR and TGR5 signaling have led to a paradigm shift in knowledge regarding bile acid physiology and metabolic health. Bile acids are now recognized as signaling molecules that orchestrate blood glucose, lipid and energy metabolism. Changes in FXR and/or TGR5 signaling modulates the secretion of gastrointestinal hormones including glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), hepatic gluconeogenesis, glycogen synthesis, energy expenditure, and the composition of the gut microbiome. These effects may contribute to the metabolic benefits of bile acid sequestrants, metformin, and bariatric surgery. This review focuses on the role of bile acids in energy intake and body weight, particularly their effects on gastrointestinal hormone secretion, the changes in obesity and T2D, and their potential relevance to the management of metabolic disorders.

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