<b>Cellular distributions of monocarboxylate transporters: a r</b><b>eview </b>

Abstract

Lactate and ketone bodies play important roles as alternative energy substrates, especially in conditions with a decreased utility of glucose. Short-chain fatty acids (acetate, propionate, and butyrate), produced by bacterial fermentation, supply most of the energy substrates in ruminants such as the cow and sheep. These monocarboxylates are transfered through the plasma membrane by proton-coupled monocarboxylate transporters (MCTs) and sodium-coupled MCTs (SMCTs). To reveal the metabolism and functional significance of monocarboxylates, the cellular localization of MCTs and SMCTs together with the expressed intensities holds great importance. This paper reviews the immunohistochemical localization of SMCTs and major MCT subtypes throughout the mammalian body. MCTs and SMCTs display a selective membrane-bound localization with porality. In contrast to the limited expression of SMCTs in the intestine and kidney, MCTs display a broader distribution pattern than GLUTs. The brain, kidney, placenta, and male genital tract express multiple subtypes of the MCT family. Determination of the cellular localization of MCTs is most controversial in the brain, possibly due to regional differences and the transcriptional modification of MCT proteins. Information on the localization of MCTs and SMCTs aids in understanding the nutrient absorption and metabolism throughout the mammalian body. In some cases, the body may use monocarboxylates as signal molecules, like hormones.

Sodium‐glucose cotransporter 2 inhibitors regulate ketone body metabolism via inter‐organ crosstalk

“…Our data revealed that gradual increases in renal and intestinal tissue BHB levels by fasting and SGLT2i co‐occurred with increased SMCT 1 and 2 expression. SMCT1 (SLC5A8) is expressed in the (mainly distal) epithelial cells lining the gastrointestinal tract and kidney proximal tubule . SMCT2 (SLC5Q12) is also expressed in renal epithelial cells all along the proximal tubule, in contrast to the restricted pattern of SMCT1, principally to the straight portion of the proximal tubule .…”

“…29,56 SMCT2 (SLC5Q12) is also expressed in renal epithelial cells all along the proximal tubule, in contrast to the restricted pattern of SMCT1, principally to the straight portion of the proximal tubule. 30 SMCT 1 and 2 may play important roles in the absorption of ketone bodies in kidney and intestine 30,56 ; of note, SMCT1 also contributes to absorption of short-chain fatty acids (SCFAs) such as butyrate, 30,31,57 an important substrate for intestinal ketogenesis. 32 In this study, BHB increased SMCT 1 and 2 in renal proximal tubular cells, and in intestinal epithelial cells both butyrate and BHB increased SMCT1 expression.…”

Free fatty acid receptor 3 activation suppresses neurogenic motility in rat proximal colon

“…Due to this lack of inhibition, FFA3‐KO mice likely malabsorb SCFA because of rapid peristalsis, limiting intraluminal fermentation and SCFA generation. 41 SCFA are the principal metabolites of microbial fermentative activity, serving as a host energy source after active absorption across the intestinal epithelium via the transport proteins SMCT and the MCTs . It is reasonable to assume that subepithelial SCFA affect enteric neurons expressing FFA3 with consequent effects on gastrointestinal functions such as ion and water secretion and absorption and peristalsis, in order to maintain host homeostasis and a healthy host‐microbial relationship.…”

Neural FFA3 activation inversely regulates anion secretion evoked by nicotinic ACh receptor activation in rat proximal colon

“…High concentrations (∼100 m m ) of mixed SCFAs are generated in the cecal lumen as a result of microbial metabolism (Bergman, ). Accordingly, the proximal colon absorbs SCFAs via monocarboxylate transporters (MCTs) as a primary colonocyte energy source and as substrates of hepatocyte metabolism (Iwanaga & Kishimoto, ). Thus, SCFA sensing in the proximal colon probably reduces motility and secretion, which facilitates fermentation of the luminal content and the absorption of luminal SCFAs.…”