Bile Acids and Metabolic Regulation: Mechanisms and clinical responses to bile acid sequestration

Aim: Examine bile acids effects in Type 2 diabetes. Background: In recent studies, the bile acid ursodeoxycholic acid (UDCA) has shown potent anti-inflammatory effects in obese patients while in type 2 diabetics (T2D) levels of the pro-inflammatory bile acid lithocholic acid were increased, and levels of the anti-inflammatory bile acid chenodeoxycholic acid were decreased, in plasma. Objective: Hence, this study aimed to examine applications of novel UDCA nanoparticles in diabetes. Methods: Diabetic balb/c adult mice were divided into three equal groups and gavaged daily with either empty microcapsules, free UDCA, or microencapsulated UDCA over two weeks. Their blood, tissues, urine, and faeces were collected for blood glucose, inflammation, and bile acid analyses. UDCA resulted in modulatory effects on bile acids profile without antidiabetic effects suggesting that bile acid modulation was not directly linked to diabetes treatment. Results: UDCA resulted in modulatory effects on bile acids profile without antidiabetic effects suggesting that bile acid modulation was not directly linked to diabetes treatment. Conclusion: Bile acids modulated the bile profile without affecting blood glucose levels.

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Physiology and Physical Chemistry of Bile Acids

International Journal of Molecular Sciences ◽

10.3390/ijms22041780 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1780

Author(s):

Maria Chiara di Gregorio ◽

Jacopo Cautela ◽

Luciano Galantini

Keyword(s):

Physical Chemistry ◽

Bile Acids ◽

Material Science ◽

Metabolic Regulation ◽

Enterohepatic Circulation ◽

Building Blocks ◽

The Body ◽

Active Molecule ◽

Supramolecular Aggregates ◽

Biological Field

Bile acids (BAs) are facial amphiphiles synthesized in the body of all vertebrates. They undergo the enterohepatic circulation: they are produced in the liver, stored in the gallbladder, released in the intestine, taken into the bloodstream and lastly re-absorbed in the liver. During this pathway, BAs are modified in their molecular structure by the action of enzymes and bacteria. Such transformations allow them to acquire the chemical–physical properties needed for fulling several activities including metabolic regulation, antimicrobial functions and solubilization of lipids in digestion. The versatility of BAs in the physiological functions has inspired their use in many bio-applications, making them important tools for active molecule delivery, metabolic disease treatments and emulsification processes in food and drug industries. Moreover, moving over the borders of the biological field, BAs have been largely investigated as building blocks for the construction of supramolecular aggregates having peculiar structural, mechanical, chemical and optical properties. The review starts with a biological analysis of the BAs functions before progressively switching to a general overview of BAs in pharmacology and medicine applications. Lastly the focus moves to the BAs use in material science.

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Manipulating the Microbiome: An Alternative Treatment for Bile Acid Diarrhoea

Microbiology Research ◽

10.3390/microbiolres12020023 ◽

2021 ◽

Vol 12 (2) ◽

pp. 335-353

Author(s):

Evette B. M. Hillman ◽

Sjoerd Rijpkema ◽

Danielle Carson ◽

Ramesh P. Arasaradnam ◽

Elizabeth M. H. Wellington ◽

...

Keyword(s):

Bile Acid ◽

Bile Acids ◽

Gastrointestinal Disease ◽

Acid Synthesis ◽

Bile Acid Synthesis ◽

Bile Acid Metabolism ◽

The United Kingdom ◽

The 1960S ◽

Irritable Bowel ◽

The Uk

Bile acid diarrhoea (BAD) is a widespread gastrointestinal disease that is often misdiagnosed as irritable bowel syndrome and is estimated to affect 1% of the United Kingdom (UK) population alone. BAD is associated with excessive bile acid synthesis secondary to a gastrointestinal or idiopathic disorder (also known as primary BAD). Current licensed treatment in the UK has undesirable effects and has been the same since BAD was first discovered in the 1960s. Bacteria are essential in transforming primary bile acids into secondary bile acids. The profile of an individual’s bile acid pool is central in bile acid homeostasis as bile acids regulate their own synthesis. Therefore, microbiome dysbiosis incurred through changes in diet, stress levels and the introduction of antibiotics may contribute to or be the cause of primary BAD. This literature review focuses on primary BAD, providing an overview of bile acid metabolism, the role of the human gut microbiome in BAD and the potential options for therapeutic intervention in primary BAD through manipulation of the microbiome.

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The economy of the enterohepatic circulation of bile acids in the baboon. 2. Regulation of bile acid synthesis by enterohepatic circulation of bile acids.

The Journal of Lipid Research ◽

10.1016/s0022-2275(20)37795-6 ◽

1984 ◽

Vol 25 (5) ◽

pp. 437-447

Author(s):

R N Redinger

Keyword(s):

Bile Acid ◽

Bile Acids ◽

Enterohepatic Circulation ◽

Acid Synthesis ◽

Bile Acid Synthesis

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Regulation of bile acid synthesis in the rat: relationship between hepatic cholesterol 7 alpha-hydroxylase activity and portal bile acids.

The Journal of Lipid Research ◽

10.1016/s0022-2275(20)39908-9 ◽

1995 ◽

Vol 36 (2) ◽

pp. 315-321

Author(s):

K Fukushima ◽

H Ichimiya ◽

H Higashijima ◽

H Yamashita ◽

S Kuroki ◽

...

Keyword(s):

Bile Acid ◽

Bile Acids ◽

Acid Synthesis ◽

Bile Acid Synthesis ◽

Hepatic Cholesterol ◽

Hydroxylase Activity

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Liver Bile Acid Changes in Mouse Models of Alzheimer’s Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22147451 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7451

Author(s):

Harpreet Kaur ◽

Drew Seeger ◽

Svetlana Golovko ◽

Mikhail Golovko ◽

Colin Kelly Combs

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Bile Acid ◽

Bile Acids ◽

Cholesterol Metabolism ◽

Amyloid Β ◽

Acid Synthesis ◽

Bile Acid Synthesis ◽

Liver Cholesterol ◽

Bile Acid Metabolism

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive cognitive impairment. It is hypothesized to develop due to the dysfunction of two major proteins, amyloid-β (Aβ) and microtubule-associated protein, tau. Evidence supports the involvement of cholesterol changes in both the generation and deposition of Aβ. This study was performed to better understand the role of liver cholesterol and bile acid metabolism in the pathophysiology of AD. We used male and female wild-type control (C57BL/6J) mice to compare to two well-characterized amyloidosis models of AD, APP/PS1, and AppNL-G-F. Both conjugated and unconjugated primary and secondary bile acids were quantified using UPLC-MS/MS from livers of control and AD mice. We also measured cholesterol and its metabolites and identified changes in levels of proteins associated with bile acid synthesis and signaling. We observed sex differences in liver cholesterol levels accompanied by differences in levels of synthesis intermediates and conjugated and unconjugated liver primary bile acids in both APP/PS1 and AppNL-G-F mice when compared to controls. Our data revealed fundamental deficiencies in cholesterol metabolism and bile acid synthesis in the livers of two different AD mouse lines. These findings strengthen the involvement of liver metabolism in the pathophysiology of AD.

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

Nutrients ◽

10.3390/nu13041104 ◽

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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Validation of Recombinant Chicken Liver Bile Acid Binding Protein as a Tool for Cholic Acid Hosting

Biomolecules ◽

10.3390/biom11050645 ◽

2021 ◽

Vol 11 (5) ◽

pp. 645

Author(s):

Giusy Tassone ◽

Maurizio Orlandini ◽

Massimo Olivucci ◽

Cecilia Pozzi

Keyword(s):

Bile Acid ◽

High Resolution ◽

Affinity Chromatography ◽

Bile Acids ◽

Drug Carriers ◽

Chicken Liver ◽

Purification Procedure ◽

Acid Binding Protein ◽

Bile Acid Binding ◽

Exogenous Substances

Bile acids (BAs) are hydroxylated steroids derived from cholesterol that act at the intestinal level to facilitate the absorption of several nutrients and also play a role as signaling molecules. In the liver of various vertebrates, the trafficking of BAs is mediated by bile acid-binding proteins (L-BABPs). The ability to host hydrophobic or amphipathic molecules makes BABPs suitable for the distribution of a variety of physiological and exogenous substances. Thus, BABPs have been proposed as drug carriers, and more recently, they have also been employed to develop innovative nanotechnology and biotechnology systems. Here, we report an efficient protocol for the production, purification, and crystallization of chicken liver BABP (cL-BABP). By means of target expression as His6-tag cL-BABP, we obtained a large amount of pure and homogeneous proteins through a simple purification procedure relying on affinity chromatography. The recombinant cL-BABP showed a raised propensity to crystallize, allowing us to obtain its structure at high resolution and, in turn, assess the structural conservation of the recombinant cL-BABP with respect to the liver-extracted protein. The results support the use of recombinant cL-BABP for the development of drug carriers, nanotechnologies, and innovative synthetic photoswitch systems.

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