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

Abstract

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.

Curdlan intake changes gut microbial composition, short-chain fatty acid production, and bile acid transformation in mice

“…This result may depend on other factors such as energy harvest, except for SCFA production by curdlan. Moreover, suppression of plasma cholesterol by curdlan supplementation may be related to changes in fecal BA profiles, because cholesterol acts as a substance for BA synthesis [ 36 ]. However, further studies using SCFA receptor-deficient mice are needed to clarify the detailed mechanism of the curdlan intake-mediated cholesterol suppression effect.…”

Decoding the Role of Gut-Microbiome in the Food Addiction Paradigm

“…Gut microbiota-derived secondary bile acids act through the nuclear farnesoid X receptor (FXR) and the Takeda G protein-coupled membrane receptor 5 (TGR5) to regulate different peripheral metabolic pathways [ 109 ]. Moreover, acting directly in hypothalamic TGR5 [ 110 ] and through diverse indirect pathways can also signal to the CNS to regulate food intake [ 111 , 112 ]. In turn, bile acid signaling can influence microbial composition [ 113 ].…”

New Insights of Anti-Hyperglycemic Agents and Traditional Chinese Medicine on Gut Microbiota in Type 2 Diabetes

“…58 The relative binding affinity of primary and secondary bile acids to FXR is variable (CDCA > DCA > LCA > CA > UDCA). 59,60 TGR5 is highly expressed in liver, gastrointestinal tract, immune cells, gallbladder and pancreas. 61 Like FXR, its relative binding affinity to primary and secondary bile acids varies substantially (LCA > DCA > CDCA > CA > UDCA).…”