TY - JOUR T1 - Bye, bye, bile: how altered bile acid composition changes small intestinal lipid sensing JF - Gut JO - Gut SP - 1549 LP - 1550 DO - 10.1136/gutjnl-2020-320873 VL - 69 IS - 9 AU - Frank A Duca AU - Tony K T Lam Y1 - 2020/09/01 UR - http://gut.bmj.com/content/69/9/1549.abstract N2 - The gastrointestinal (GI) tract is increasingly recognised as a major contributor to energy homoeostasis that impact obesity progression. The gut represents the first site of interaction between incoming nutrients and the host, generating crucial negative feedback signalling to regulate food intake possibly by altering GI function like gastric emptying. In the case of proximal intestinal lipid sensing, several mechanisms have been identified to drive both satiety and satiation. For example, dietary fat is hydrolysed and absorbed into enterocytes. In the upper GI, this stimulates the synthesis of oleoylethanolamide (OEA), which can then act as a signalling molecule to induce satiety via activation of peroxisome proliferator-activated receptor-α and a gut-brain axis.1 Alternatively, activation of enteroendocrine cells (EECs) by free fatty acids binding to G protein-coupled receptor-40 leads to secretion of gut peptides, like cholecystokinin and glucagon-like peptide-1 (GLP-1), which slow gastric emptying and reduce food intake. Interestingly, activation of EECs via free fatty acids is hypothesised to occur on the basolateral side, requiring chylomicron formation, and thus dietary fat hydrolysis, similar to OEA production.2 Given that bile acids, especially cholic acid in mice, emulsify dietary lipids and thus promote efficient hydrolysis and absorption of lipids in the small intestine, their function would implicate a necessity in activating the aforementioned pathways to lower food intake.In GUT, Higuchi et al observed that Cyp8b1-/- mice exhibited reduced body weight and adiposity due to an inhibition of food intake. As expected, lowering cholic acid and other 12α-hydroxylated bile acids via … ER -