scholarly journals Cholesterol Feeding Prevents Hepatic Accumulation of Bile Acids in Cholic Acid-Fed Farnesoid X Receptor (FXR)-Null Mice: FXR-Independent Suppression of Intestinal Bile Acid Absorption

2008 ◽  
Vol 37 (2) ◽  
pp. 338-344 ◽  
Author(s):  
Masaaki Miyata ◽  
Yoshiki Matsuda ◽  
Masahiro Nomoto ◽  
Yuki Takamatsu ◽  
Nozomi Sato ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Cholic Acid ◽  
Farnesoid X Receptor ◽  
Cholesterol Feeding ◽  
Acid Absorption ◽  
Bile Acid Absorption

Weanling, but not adult, rabbit colon absorbs bile acids: flux is linked to expression of putative bile acid transporters

2006 ◽  
Vol 290 (3) ◽  
pp. G439-G450 ◽  
Author(s):  
Dirk Weihrauch ◽  
Jainuch Kanchanapoo ◽  
Mei Ao ◽  
Roli Prasad ◽  
Pawinee Piyachaturawat ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Short Circuit ◽  
Distal Colon ◽  
Lipid Binding ◽  
Farnesoid X Receptor ◽  
Acid Transport ◽  
Bile Acid Transport ◽  
Acid Absorption ◽  
Bile Acid Absorption

Intestinal handling of bile acids is age dependent; adult, but not newborn, ileum absorbs bile acids, and adult, but not weanling or newborn, distal colon secretes Cl− in response to bile acids. Bile acid transport involving the apical Na+-dependent bile acid transporter (Asbt) and lipid-binding protein (LBP) is well characterized in the ileum, but little is known about colonic bile acid transport. We investigated colonic bile acid transport and the nature of the underlying transporters and receptors. Colon from adult, weanling, and newborn rabbits was screened by semiquantitative RT-PCR for Asbt, its truncated variant t-Asbt, LBP, multidrug resistance-associated protein 3, organic solute transporter-α, and farnesoid X receptor. Asbt and LBP showed maximal expression in weanling and significantly less expression in adult and newborn rabbits. The ileum, but not the colon, expressed t-Asbt. Asbt, LBP, and farnesoid X receptor mRNA expression in weanling colon parallel the profile in adult ileum, a tissue designed for high bile acid absorption. To examine their functional role, transepithelial [3H]taurocholate transport was measured in weanling and adult colon and ileum. Under short-circuit conditions, weanling colon and ileum and adult ileum showed net bile acid absorption: 1.23 ± 0.62, 5.53 ± 1.20, and 11.41 ± 3.45 nmol·cm−2·h−1, respectively. However, adult colon secreted bile acids (−1.39 ± 0.47 nmol·cm−2·h−1). We demonstrate for the first time that weanling, but not adult, distal colon shows net bile acid absorption. Thus increased expression of Asbt and LBP in weanling colon, which is associated with parallel increases in taurocholate absorption, has relevance in enterohepatic conservation of bile acids when ileal bile acid recycling is not fully developed.

scholarly journals Mechanism of Dyslipidemia in Obesity—Unique Regulation of Ileal Villus Cell Brush Border Membrane Sodium–Bile Acid Cotransport

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1197 ◽  
Author(s):  
Sundaram ◽  
Palaniappan ◽  
Nepal ◽  
Chaffins ◽  
Sundaram ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Brush Border ◽  
Dietary Fat ◽  
Brush Border Membrane ◽  
Farnesoid X Receptor ◽  
Bile Acid Absorption ◽  
Associated Proteins ◽  
Villus Cell ◽  
Stimulation Of

In obesity, increased absorption of dietary fat contributes to altered lipid homeostasis. In turn, dyslipidemia of obesity leads to many of the complications of obesity. Bile acids are necessary for the absorption of dietary fat. In the mammalian intestine, apical sodium-dependent bile acid cotransporter (ASBT; SLC10A2) is exclusively responsible for the reabsorption of bile acids in the terminal ileum. In rat and mice models of obesity and importantly in obese humans, ASBT was increased in ileal villus cells. The mechanism of stimulation of ASBT was secondary to an increase in ASBT expression in villus cell brush border membrane. The stimulation of ASBT was not secondary to the altered Na-extruding capacity of villus cells during obesity. Further, increased Farnesoid X receptor (FXR) expression in villus cells during obesity likely mediated the increase in ASBT. Moreover, enhanced FXR expression increased the expression of bile-acid-associated proteins (IBABP and OSTα) that are responsible for handling bile acids absorbed via ASBT in villus cells during obesity. Thus, this study demonstrated that in an epidemic condition, obesity, the dyslipidemia that leads to many of the complications of the condition, may, at least in part, be due to deregulation of intestinal bile acid absorption.

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.

scholarly journals Recent advances in understanding bile acid homeostasis

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 2029 ◽  
Author(s):  
John YL Chiang
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Farnesoid X Receptor ◽  
Recent Advances ◽  
Bile Acid Pool Size ◽  
Bile Acid Receptor ◽  
Acid Toxicity ◽  
G Protein Coupled

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.

scholarly journals Effect of ursodeoxycholic acid on lipid metabolism: through the prism of evidence from 2019.

2020 ◽  
Vol 46 (1) ◽  
pp. 83-88
Author(s):  
N. B. Gubergrits ◽  
N.V. Byelyayeva ◽  
T. L. Mozhyna ◽  
G. M. Lukashevich ◽  
P. G. Fomenko
Keyword(s):  
Lipid Metabolism ◽  
Bile Acid ◽  
Bile Acids ◽  
De Novo ◽  
Gallstone Disease ◽  
Farnesoid X Receptor ◽  
Synthesis Rate ◽  
Primary Biliary Cholangitis ◽  
Fractional Synthesis Rate ◽  
Fractional Synthesis

After the discovery of the method of ursodeoxycholic acid’s (UDCA) synthesis and the publication of evidence confirming its ability to reduce the lithogenic properties of bile, active clinical use of UDCA began in the world. This drug, which has pleiotropic effect (choleretic, cytoprotective, immunomodulatory, antiapoptic, litholytic, hypocholesterolemic), has proven its effectiveness in the treatment various diseases: primary biliary cholangitis, intrahepatic cholestasis of pregnancy, gallstone disease. Being a tertiary bile acid, UDCA stimulates bile acid synthesis by reducing the circulating fibroblast growth factor 19 and inhibiting the activation of the farnesoid X-receptor (FXR), which leads to the induction of cholesterol-7α-hydroxylase, a key enzyme in the synthesis of bile acid de novo, mediating the conversion of cholesterol into bile acids. Changes in the formation of bile acids and cholesterol while taking UDCA intake is accompanied by activation of the main enzyme of cholesterol synthesis - 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). Under the influence of UDCA the activity of stearoyl-Coa desaturase (SCD) in visceral white adipose tissue increases. According to studies conducted in 2019, UDCA improves lipid metabolism by regulating the activity of the ACT/mTOR signaling pathway, reduces the synthesis of cholesterol, decreases the fractional synthesis rate of cholesterol and the fractional synthesis rate of triglycerides. It has been proved that UDCA is accompanied by a decrease in the level of total cholesterol and low density lipoprotein cholesterol.

scholarly journals Arbutin Alleviates the Liver Injury of α-Naphthylisothiocyanate-induced Cholestasis Through Farnesoid X Receptor Activation

2021 ◽  
Vol 9 ◽  
Author(s):  
Peijie Wu ◽  
Ling Qiao ◽  
Han Yu ◽  
Hui Ming ◽  
Chao Liu ◽  
...  
Keyword(s):  
Bile Acid ◽  
Liver Injury ◽  
Protective Effect ◽  
Bile Acids ◽  
Liver Toxicity ◽  
Enterohepatic Circulation ◽  
Receptor Activation ◽  
Farnesoid X Receptor ◽  
Bile Acid Metabolism ◽  
Cholestatic Diseases

Cholestasis is a kind of stressful syndrome along with liver toxicity, which has been demonstrated to be related to fibrosis, cirrhosis, even cholangiocellular or hepatocellular carcinomas. Cholestasis usually caused by the dysregulated metabolism of bile acids that possess high cellular toxicity and synthesized by cholesterol in the liver to undergo enterohepatic circulation. In cholestasis, the accumulation of bile acids in the liver causes biliary and hepatocyte injury, oxidative stress, and inflammation. The farnesoid X receptor (FXR) is regarded as a bile acid–activated receptor that regulates a network of genes involved in bile acid metabolism, providing a new therapeutic target to treat cholestatic diseases. Arbutin is a glycosylated hydroquinone isolated from medicinal plants in the genus Arctostaphylos, which has a variety of potentially pharmacological properties, such as anti-inflammatory, antihyperlipidemic, antiviral, antihyperglycemic, and antioxidant activity. However, the mechanistic contributions of arbutin to alleviate liver injury of cholestasis, especially its role on bile acid homeostasis via nuclear receptors, have not been fully elucidated. In this study, we demonstrate that arbutin has a protective effect on α-naphthylisothiocyanate–induced cholestasis via upregulation of the levels of FXR and downstream enzymes associated with bile acid homeostasis such as Bsep, Ntcp, and Sult2a1, as well as Ugt1a1. Furthermore, the regulation of these functional proteins related to bile acid homeostasis by arbutin could be alleviated by FXR silencing in L-02 cells. In conclusion, a protective effect could be supported by arbutin to alleviate ANIT-induced cholestatic liver toxicity, which was partly through the FXR pathway, suggesting arbutin may be a potential chemical molecule for the cholestatic disease.

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