ABSTRACT
Bile acids are the main products of the cholesterol degradation in the liver. They promote the absorption and transportation of the intestinal lipids. Diverse bile acid receptors are widely distributed in human tissues and organs, including farnesoid X receptor (FXR) and Takeda G protein receptor (TGR5). The expression pattern of different bile acid receptors and their different affinities to various bile acids as their ligands determines their pleiotropic downstream effects, including regulating bile acid synthesis and transportation, immune and metabolism homeostasis. In addition, the bile acid pool includes components derived from both host and gut microbiota, which collaboratively contribute to the bile acid signaling activation in different compartments. Therefore, bile acid pool represents an information hub allowing the crosstalk between the host and gut microbiome and hereby modulating host metabolic homeostasis and gut microbiome symbiosis. This article reviews the recent advances in the field of bile acid regulation and the related mechanisms of bile acid signaling pathway to maintain metabolic homeostasis.
ABSTRACT
Objective::To investigate the protective effect of modified Yinchenhao Tang on α-isothiocyanate(ANIT)-induced cholestatic liver disease (CSLD). Method::Wistar rats were randomly divided into 7 groups: blank control group, model control group, compound Glycyrrhizin capsules group(22.5, 45 mg·kg-1), modified Yinchenhao Tang low, middle and high dose groups(4.1, 8.1, 16.2 g·kg-1). A model of cholestatic liver injury was prepared by intragastric administration of ANIT (100 mg·kg-1). Glycyrrhizin capsules and modified Yinchenhao Tang were administered intragastrically on the second day of modeling for 4 consecutive days. And bile duct intubation was performed on the fifth day to measure the bile flow rate of the rats, and serum was taken to test the total bilirubin(TBIL), direct bilirubin(DBIL), indirect bilirubin(IBIL), alanine aminotransferase(ALT) and total bile acid(TBA) serological indicators of each group. Pathological changes of liver tissues were observed by hematoxylin-eosin (HE) staining. The expression levels of G protein-coupled bile acid receptor(TGR5), nucleotide binding oligomerization domain-like receptor 3(NLRP3) and cysteinyl aspartate specific proteinase-1(Caspase-1) proteins in the iver tissues were detected by Western blot. Result::Compared with the blank control group, bile flow rate in the model group decreased significantly(P<0.01). TBIL, DBIL, IBIL, ALT and TBA level in serum were significantly increased(P<0.01), liver tissue lesions were severe, and significantly increased the expression of liver tissue TGR5 and Caspase-1.Compare with model group, the compound Glycyrrhizin capsules group had no significant effect on bile flow rate and TBIL, DBIL, IBIL, ALT and TBA level in serum. Bile flow rate increased and TBIL, DBIL, IBIL, ALT and TBA level in serum decreased significantly in modified Yinchenhao Tang high dose group. The compound Glycyrrhizin capsules group and modified Yinchenhao Tang group have different extents of improvement the pathological changes of the lung tissues, and the protein expression of TGR5 and Caspase-1 were significantly decreased in the liver tissue(P<0.01). Conclusion::Modified Yinchenhao Tang can effectively treat CSLD in rats, and its mechanism may be related to bile acid and bile acid receptor TGR5-mediated inflammatory factors.
ABSTRACT
Bile acid as a signaling molecule can specifically bind to bile acid receptors (such as farnesoid X receptor and G-protein-coupled bile acid receptor) to mediate a series of biological regulation reactions. In recent years, it has been found that bile acids are widely involved in glucose metabolism, lipid metabolism and energy metabolism. The development of metabolic diseases is usually accompanied by the changes of bile acid profiles and receptors, and thus bile acids may be applied as potential biomarkers for clinical diagnosis, prediction, and evaluation of therapeutic effects. This article reviews the relationship between bile acids and metabolic diseases, and the treatment of metabolic diseases based on the regulation of bile acid metabolism.
ABSTRACT
Bile acids (BAs) are originally known as detergents essential for the digestion and absorption of lipids. In recent years, extensive research has unveiled new functions of BAs as gut hormones that modulate physiological and pathological processes, including glucose and lipid metabolism, energy expenditure, inflammation, tumorigenesis, cardiovascular disease, and even the central nervous system in addition to cholesterol homeostasis, enterohepatic protection and liver regeneration. BAs are closely linked with gut microbiota which might explain some of their crucial roles in organs. The signaling actions of BAs can also be mediated through specific nuclear receptors and membrane-bound G protein-coupled receptors. Several pharmacological agents or bariatric surgeries have demonstrated efficacious therapeutic effects on metabolic diseases through targeting BA signaling. In this mini-review, we summarize recent advances in bile-ology, focusing on its translational studies.
ABSTRACT
Bile acids (BAs) are originally known as detergents essential for the digestion and absorption of lipids. In recent years, extensive research has unveiled new functions of BAs as gut hormones that modulate physiological and pathological processes, including glucose and lipid metabolism, energy expenditure, inflammation, tumorigenesis, cardiovascular disease, and even the central nervous system in addition to cholesterol homeostasis, enterohepatic protection and liver regeneration. BAs are closely linked with gut microbiota which might explain some of their crucial roles in organs. The signaling actions of BAs can also be mediated through specific nuclear receptors and membrane-bound G protein-coupled receptors. Several pharmacological agents or bariatric surgeries have demonstrated efficacious therapeutic effects on metabolic diseases through targeting BA signaling. In this mini-review, we summarize recent advances in bile-ology, focusing on its translational studies.
ABSTRACT
Though bile acids have been well known as digestive juice, recent studies have demonstrated that bile acids bind to their endogenous receptors, including Farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (GPBAR1; TGR5) and serve as hormone to control various biological processes, including cholesterol/bile acid metabolism, glucose/lipid metabolism, immune responses, and energy metabolism. Deficiency of those bile acid receptors has been reported to induce diverse metabolic syndromes such as obesity, hyperlipidemia, hyperglycemia, and insulin resistance. As consistent, numerous studies have reported alteration of bile acid signaling pathways in type II diabetes patients. Interestingly, bile acids have shown to activate TGR5 in intestinal L cells and enhance secretion of glucagon-like peptide 1 (GLP-1) to potentiate insulin secretion in response to glucose. Moreover, FXR has been shown to crosstalk with TGR5 to control GLP-1 secretion. Altogether, bile acid receptors, FXR and TGR5 are potent therapeutic targets for the treatment of metabolic diseases, including type II diabetes.
Subject(s)
Humans , Bile , Bile Acids and Salts , Biological Phenomena , Energy Metabolism , Enteroendocrine Cells , Glucagon-Like Peptide 1 , Glucose , Homeostasis , Hyperglycemia , Hyperlipidemias , Insulin , Insulin Resistance , Metabolic Diseases , Metabolism , ObesityABSTRACT
Bile acids, as one of the constituents of bile, can promote the digestion and absorption of fat and cholesterol metabolism. Studies find that bile acid is a signal molecule that not only combines with nuclear hormone receptors such as farnesoid X receptor, and G protein coupled bile acid receptor 5, to regulate their own metabolism, but also plays an important role in diabetes, obesity, non-alcoholic fatty liver disease and other metabolic diseases. The research on its mechanism will provide a solid theoretical basis for the diagnosis and treatment of metabolic diseases. In this review, we summarized the research progress of bile acids in glucolipid metabolic diseases.
ABSTRACT
With recent developments, biologic therapies has shown superior efficacy for rheumatic diseases compared with preexisting pharmacologic therapies, which are associated with high costs, non-response in certain patient groups, and severe adverse effects such as infections limiting their wide-spread use and revealing a need for the development of novel treatments. Since discovering the role of bile acid receptors in regulating inflammation, clinical trials evaluating the use of bile acid receptor agonists as a means to potentially treat various inflammatory disorders, such as alcoholic hepatitis, non-alcoholic steatohepatitis, primary biliary cirrhosis, primary sclerosing cholangitis have been ongoing. This review summarizes the results of studies on the anti-inflammatory effects and mechanisms of bile acid receptors and the results of previous to date looking at the use of bile acid receptor agonists in animal models of inflammatory disorders and clinical trials. Furthermore, we present the potentials of the bile acid receptor agonists in the treatment of inflammatory rheumatic diseases, including rheumatoid arthritis.