SCFA transport in rat duodenum.
Bacterial or ingested food-derived short-chain fatty acids (SCFAs) are present in the duodenal lumen. Acetate, the most abundant SCFA in the foregut lumen, is absorbed immediately after ingestion, although the mechanism by which this absorption occurs is not fully understood. We investigated the distribution and function of candidate SCFA transporters in rat duodenum. The Na(+)-coupled monocarboxylate transporter-1 (SMCT1) was localized to the brush border, whereas the pH-dependent monocarboxylate transporter (MCT) 1 and MCT4 were localized to the duodenocyte basolateral membrane. In Ussing chambered duodenal mucosa, luminal acetate dose-dependently increased short-circuit current (Isc) in the presence of serosal bumetanide and indomethacin by a luminal Na(+)-dependent, ouabain-sensitive mechanism. The Isc response was inhibited dose-dependently by the SMCT1 nonsubstrate inhibitor ibuprofen, consistent with net electrogenic absorption of acetate via SMCT1. Other SCFAs and lactate also increased Isc. Furthermore, duodenal loop perfusion of acetate increased portal venous acetate concentration, inhibited by coperfusion of ibuprofen or a MCT inhibitor. Luminal acetate perfusion increased duodenal HCO3 (-) secretion via capsaicin-sensitive afferent nerve activation and cyclooxygenase activity, consistent with absorption-mediated HCO3 (-) secretion. These results suggest that absorption of luminal SCFA via SMCT1 and MCTs increases duodenal HCO3 (-) secretion. In addition to SCFA sensing via free fatty acid receptors, the presence of rapid duodenal SCFA absorption may be important for the suppression of luminal bacterial colonization and implicated in the generation of functional dyspepsia due to bacterial overgrowth.
Department of Medicine, School of Medicine, University of California, Los Angeles, Los Angeles, California; Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo, Japan; and Brentwood Biomedical Research Institute, Los Angeles, California.
Izumi
I
Kaji
Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo, Japan; and.
Toshihiko
T
Iwanaga
Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo, Japan; and.
Masahiko
M
Watanabe
Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, California; Department of Medicine, School of Medicine, University of California, Los Angeles, Los Angeles, California;
Paul H
PH
Guth
Department of Biomathematics, School of Medicine, University of California, Los Angeles, Los Angeles, California;
Eli
E
Engel
Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, California; Department of Medicine, School of Medicine, University of California, Los Angeles, Los Angeles, California; Department of Surgery, School of Medicine, University of California, Los Angeles, Los Angeles, California; Brentwood Biomedical Research Institute, Los Angeles, California jake@ucla.edu.
Jonathan D
JD
Kaunitz
Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, California; Department of Medicine, School of Medicine, University of California, Los Angeles, Los Angeles, California; Brentwood Biomedical Research Institute, Los Angeles, California.
Yasutada
Y
Akiba
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004386:Duodenum / Q000378:metabolism*; D005232:Fatty Acids, Volatile / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D023421:Models, Animal; D011422:Propionates / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*
D005232:Fatty Acids, Volatile; D011422:Propionates; D012964:Sodium
acetate; monocarboxylate transporter; short-chain fatty acid; sodium-coupled monocarboxylate transporter