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Bye, bye, bile: how altered bile acid composition changes small intestinal lipid sensing
  1. Frank A Duca1,2,
  2. Tony K T Lam3,4
  1. 1 BIO5 Institute, University of Arizona, Tucson, Arizona, USA
  2. 2 School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, Arizona, USA
  3. 3 Toronto General Research Institute, Toronto, Ontario, Canada
  4. 4 Physiology, University of Toronto, Toronto, Ontario, Canada
  1. Correspondence to Dr Tony K T Lam, Toronto General Research Institute, Toronto, ON M5G 1L7, Canada; tony.lam{at}uhnresearch.ca; Dr Frank A Duca, BIO5 Institute, University of Arizona, Tucson, Arizona; faduca{at}email.arizona.edu

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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 …

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Footnotes

  • Twitter @TKTLam

  • Contributors The Commentary is written by FAD and edited by TKTL.

  • Funding FAD is funded by the National Institutes of Health (NIH-1R01DK121804) and United States Department of Agriculture (USDA) - National Institute of Food and Agriculture (NIFA) (2019-67017-29252). TKTL laboratory is supported by a CIHR Foundation Grant (FDN-143204). TKTL holds the John Kitson McIvor (1915-1942) Endowed Chair in Diabetes Research and the Tier 1 Canada Research Chair in Diabetes and Obesity at the Toronto General Hospital Research Institute and the University of Toronto.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Commissioned; internally peer reviewed.

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