The role of bile acids in metabolic regulation

Abstract

Bile acids (BA), long believed to only have lipid-digestive functions, have emerged as novel metabolic modulators. They have important endocrine effects through multiple cytoplasmic as well as nuclear receptors in various organs and tissues. BA affect multiple functions to control energy homeostasis, as well as glucose and lipid metabolism, predominantly by activating the nuclear farnesoid X receptor and the cytoplasmic G protein-coupled BA receptor TGR5 in a variety of tissues. However, BA also are aimed at many other cellular targets in a wide array of organs and cell compartments. Their role in the pathogenesis of diabetes, obesity and other 'diseases of civilization' becomes even more clear. They also interact with the gut microbiome, with important clinical implications, further extending the complexity of their biological functions. Therefore, it is not surprising that BA metabolism is substantially modulated by bariatric surgery, a phenomenon contributing favorably to the therapeutic effects of these surgical procedures. Based on these data, several therapeutic approaches to ameliorate obesity and diabetes have been proposed to affect the cellular targets of BA.

Saxagliptin alters bile acid profiles and yields metabolic benefits in drug‐naïve overweight or obese type 2 diabetes patient

“…Glucose tolerance and GLP‐1 secretion are impaired in TGR5 −/− mice, and activation of TGR5 by INT‐777 enhanced mitochondrial function in muscle, brown adipose tissue, and enteroendocrine cells, resulting in an increase in energy expenditure and incretin secretion . In addition, bile acids affect glucose metabolism and insulin sensitivity via TGR5‐mediated stimulation of intestinal secretion of GLP‐1 . Cholic acid supplementation increased energy expenditure and reduced weight gain by binding with TGR5 .…”

Plasma metabolite abundances are associated with urinary enterolactone excretion in healthy participants on controlled diets

“…Importantly, changes in deoxycholic acid and other bile acids can delineate metabolic diseases or conditions. 79–81 …”

Gastrointestinal Complications of Obesity

“…In the past, it was thought that the small intestine played a passive role, simply absorbing the excess calories ingested by obese people. Bile acids play a critically important role in the absorption of fats; the role of bile acids in metabolic regulation 52 or as potential therapeutic approaches for obesity and metabolic syndrome 53 are beyond the scope of this article; however, there is no evidence that bile acid synthesis or enterohepatic circulation is altered by obesity. On the other hand, there is evidence that the small intestine is able to adapt its absorptive functions for the 3 macronutrient classes, as follows: (1) lipid absorption capacity adapts to the fat content of the diet, especially through the coordinated induction of lipid binding proteins, which are involved in the intestinal absorption of long-chain fatty acids as well as their uptake, trafficking, and re-assembly into chylomicrons 54 ; (2) energy intake from infusion of intraduodenal whey protein hydrolysate tended to be higher in obese nondiabetic men than in lean controls 55 ; and (3) in morbid obesity, glucose absorption in the proximal intestine is accelerated and this is related to increased sodium-glucose linked transporter-1 (SGLT-1) expression.…”