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Short-chain fatty acid sensing in rat duodenum.

Yasutada Akiba1, Takuya Inoue, Izumi Kaji

  • 1Greater Los Angeles Veterans Affairs Healthcare System, 11301 Wilshire Boulevard, Los Angeles, CA, 90073, USA; Department of Medicine, University of California, Los Angeles, CA, 90095, USA; Brentwood Biomedical Research Institute, 11301 Wilshire Blvd, Los Angeles, CA, 90073, USA.

The Journal of Physiology
|November 30, 2014
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Summary

Short-chain fatty acids (SCFAs) in the duodenum activate specific receptors, influencing gut hormone release and potentially contributing to functional dyspepsia symptoms. This study elucidates the mechanisms of SCFA action on duodenal secretion and hormone pathways.

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Area of Science:

  • Gastroenterology
  • Neurogastroenterology
  • Molecular Gastronomy

Background:

  • Intraduodenal fatty acids (FA) and bacterial overgrowth, generating short-chain fatty acids (SCFAs), are linked to functional dyspepsia.
  • The role of luminal SCFAs in the foregut on gastroduodenal function remains unclear.

Purpose of the Study:

  • To investigate the mechanisms by which luminal SCFA perfusion influences duodenal bicarbonate secretion (DBS).
  • To identify the specific free fatty acid receptors (FFARs) involved in mediating SCFA effects in the duodenum.

Main Methods:

  • Immunolocalization of FFARs (FFA1, FFA2, FFA3) in duodenal enteroendocrine cells.
  • Luminal perfusion of SCFAs (acetate, propionate) and selective FFAR agonists in the duodenum.
  • Measurement of DBS, portal blood concentrations of glucagon-like peptide-2 (GLP-2), and effects of receptor antagonists and inhibitors.

Main Results:

  • Luminal SCFAs (acetate, propionate) increased DBS and GLP-2 concentrations.
  • FFA1 activation increased DBS via GLP-2 release, while FFA2 activation stimulated DBS through muscarinic and 5-HT4 receptors.
  • SCFA/HCO3(-) exchange was also observed in the duodenum.

Conclusions:

  • Duodenal fatty acid sensing receptors mediate hormone release and neural activation, implicating SCFAs in functional dyspepsia pathogenesis.
  • Luminal SCFAs modulate gastroduodenal functions via distinct receptor pathways (FFA1/FFA3-GLP-2 and FFA2-muscarinic/5-HT4).