The relationship between postprandial bile acid concentration, GLP‐1, PYY and ghrelin

Abstract

Summary Background Gut hormones peptide YY (PYY) and glucagon‐like peptide‐1 (GLP‐1) play an integral role in appetite control and energy homeostasis. Entero‐endocrine L‐cells can be stimulated by nutrients and or bile acids to co‐secrete PYY and GLP‐1. The aim of this study was to determine the response of bile acids, PYY, GLP‐1 and ghrelin after a test meal. Design Twelve subjects with a BMI of 22·8 (0·52) kg/m2 [mean (SEM)] received a 400 kcal test meal after which blood samples were taken every 30 min from 0 to 180 min. PYY, GLP‐1 and ghrelin were measured by radioimmunoassays. Fractionated bile acids were measured by HPLC‐MSMS. Results PYY positively correlated with glycochenodeoxycholic acid (GCDCA) (rs = 0·23, P = 0·03) and taurochenodeoxycholic acid (TCDCA) (rs = 0·26, P = 0·02). GLP‐1 positively correlated with GCDCA (rs = 0·22, P = 0·047) and glycodeoxycholic acid (GDCA) (rs = 0·3, P = 0·005). Ghrelin negatively correlated with GDCA (rs = −0·45, P≤ 0·0001), TCDCA (rs = −0·23, P = 0·034) and taurodeoxycholic acid (TDCA) (rs = −0·44, P≤ 0·0001). Conclusion PYY and GLP‐1 responses correlated with chenodeoxycholic acid (CDCA) counterparts, whereas ghrelin negatively correlated with deoxycholic acid (DCA) counterparts. Specific bile acids may thus differentially affect entero‐endocrine cells.

Investigating the effects of physiological bile acids on GLP-1 secretion and glucose tolerance in normal and GLP-1R-/- mice

“…There have been several recent reports linking bile acids to physiological glucose regulation (Han et al, 2004;Watanabe et al, 2006;Sato et al, 2007;Fonseca et al, 2008;Goldberg et al, 2008;Shaham et al, 2008;Roberts et al, 2011). Postprandial increases in bile acid concentrations have been reported in human volunteers after ingestion of a standard liquid meal (De Barros et al, 1982).…”

“…Furthermore, individuals with impaired glucose tolerance and high fasting insulin levels exhibited a blunted excursion of glycochenodeoxycholic acid (Shaham et al, 2008). Postprandial bile acid responses in humans appear to correlate tightly with plasma GLP-1 levels (Roberts et al, 2011). Feeding high-fat fed mice a bile acid-enriched diet for 9 weeks prevented the onset of hyperglycaemia, obesity and insulin resistance (Ikemoto et al, 1997).…”

Higher circulating bile acid concentrations in obese patients with type 2 diabetes

“…12 It is not known whether the TGR5 signalling cascade to BA is altered in patients with T2DM. Cariou et al 13 showed that plasma chenodeoxycholic acid (CDC), cholic acid (CA) and to a lesser extent DC negatively correlated with insulin sensitivity in healthy individuals, obese and T2DM patients.…”

Physiological Mechanisms behind Roux-en-Y Gastric Bypass Surgery

“…At present, it is however unclear if the increased expression of preproglucagon and PYY and secretion of GLP-1 and PYY are directly linked to an increased delivery of bile acids to L-cells in the common channel; this has not yet been studied or compared between RYGB and sham-operated rats. Unfortunately, specific antagonists of the bile acid receptor (TGR5, also called GPBAR1 [G protein-coupled bile acid receptor 1]) that mediates increased L-cell secretions [28,29] are not available, and to our knowledge, respective experiments with RYGB-operated TGR5 knockout mice have not been performed yet.…”

“…Considering the findings discussed above that the total number of L-cells is actually much higher in more proximal small intestinal segments (hence in the alimentary limb of RYGB animals), undiluted nutrients in the alimentary limb may also well be responsible for higher secretions of GLP-1, PYY and perhaps CCK. Additionally, undiluted bile acid secretions reaching the common limb via the biliopancreatic limb of RYGB animals may play an important role because it is well documented that luminal bile acids directly stimulate L-cell secretion [28,29] . At present, it is however unclear if the increased expression of preproglucagon and PYY and secretion of GLP-1 and PYY are directly linked to an increased delivery of bile acids to L-cells in the common channel; this has not yet been studied or compared between RYGB and sham-operated rats.…”