BookStefano Fiorucci, Eleonora Distrutti, editors.
Summary: This book focusses on the latest results related to the field of bile acids as signaling molecules and describes how these receptors have become a major pharmacological target. It covers all major areas of research in this field, from genetics, chemistry, in silico modeling, molecular biology to clinical applications, offering a cross-country view of the functional role of bile acids as signaling molecules, virtually acting on all major areas of metabolism. While FXR and GPBAR1 are essential bile acid sensors that integrate the de novo bile acid synthesis with intestinal microbiota and liver metabolism, in a broader sense, BARs play a pathogenic role in the development of common human alignments including liver, intestinal and metabolic disorders, such as steatosis (NAFLD) and steato-hepatitis (NASH), diabetes, obesity and atherosclerosis.
Contents:
Intro; Preface; Contents; The Pharmacology of Bile Acids and Their Receptors; 1 Introduction; 2 Bile Acids, a Family of Unconventional Steroids; 3 Bile Acids Before the Discovery of Their Receptors; 4 The Discovery of the Bile Acid-Activated Receptors: FXR and Other Nuclear Receptors; 4.1 FXR, the Bile Acid Sensor in Drug Discovery: 1999-2019; 5 Secondary Bile Acids and GPBAR1; 6 Conclusions; References; Bile Acid-Activated Receptors: GPBAR1 (TGR5) and Other G Protein-Coupled Receptors; 1 Introduction; 2 TGR5 and S1PR2 Signaling Pathways; 3 Tissue Distribution of TGR5 and S1PR2 12 Role in Advanced Liver Disease: Potential Therapeutic Target?13 Summary and Perspectives; References; Bile Acid-Activated Receptors: A Review on FXR and Other Nuclear Receptors; 1 Introduction; 2 Bile Acid-Activated Receptor Farnesoid X Receptor (FXR, NR1H4); 2.1 FXR and Bile Acid Metabolism; 2.2 FXR and Lipid Metabolism; 2.3 FXR and Glucose Metabolism; 2.4 FXR as a Therapeutic Target; 3 Bile Acids and Small Heterodimer Partner (SHP, NR0B2); 3.1 SHP and Bile Acid Metabolism; 3.2 SHP and Lipid Metabolism; 3.3 SHP and Glucose Metabolism 4 Bile Acid-Activated Receptor Pregnane X Receptor (PXR, NR1I2)4.1 PXR and Bile Acid Metabolism; 4.2 PXR and Lipid Metabolism; 4.3 PXR and Glucose Metabolism; 5 Bile Acids and Constitutive Androstane Receptor (CAR, NR1I3); 5.1 CAR and Bile Acid Metabolism; 5.2 CAR and Lipid Metabolism; 5.3 CAR and Glucose Metabolism; 6 Bile Acid-Activated Receptor Vitamin D Receptor (VDR, NR1l1); 7 Conclusions and Perspectives; References; The Enterokine Fibroblast Growth Factor 15/19 in Bile Acid Metabolism; 1 FGF Family; 2 Endocrine FGFs; 3 FGF15/FGF19 in Energy Homeostasis 4 Role of FGF15/FGF19 in the Gut-Liver Axis5 FGF19 and Hepatic Diseases; 6 FGF19-Based Therapy: Promising Reality; References; Signaling from Intestine to the Host: How Bile Acids Regulate Intestinal and Liver Immunity; 1 Bile Acids and Intestinal Microbiota; 2 Bile Acids and Immune System; 2.1 Role of Bile Acids in the Regulation of Intestinal and Liver Immunity; 2.2 Immune-Regulatory Effects of Bile Acids in Myeloid Cells: Monocytes/Macrophages and Dendritic Cells; 2.3 Immune-Regulatory Effects of Bile Acids in Lymphoid Cells; References 4 Role of S1PR2 Signaling in Hepatocytes5 Role of S1PR2 and TGR5 in Liver Sinusoidal Endothelial Cells (LSECs); 6 Role of S1PR2 and TGR5 in Hepatic Stellate Cells (HSCs) and Hepatic Myofibroblasts (hMFs); 7 Role of S1PR2 and TGR5 in Macrophages; 8 Role of S1PR2 and TGR5 in Biliary Epithelial Cells; 9 Loss of S1PR2 and TGR5 in Mice and Humans: Contribution to Liver Disease?; 10 S1PR2 and TGR5 in Cholestatic and Biliary Diseases: Pathogenetic Role and Potential Therapeutic Target?; 11 S1PR2 and TGR5 Metabolic Liver Diseases: Potential Therapeutic Target?