Dietary pectin up‐regulates monocaboxylate transporter 1 in the rat gastrointestinal tract

Abstract

This work was undertaken to study the effect of pectin feeding on the expression level, cellular localization and functional activity of monocarboxylate transporter 1 (MCT1) in the gastrointestinal tract of rats. The results indicated that MCT1 protein level was significantly increased along the entire length of the gastrointestinal tract of pectin-fed rats in comparison with control animals. Immunohistochemical analysis revealed an increase in MCT1 in the stratified squamous epithelia of the forestomach as well as in the basolateral membranes of the cells lining the gastric pit of the glandular stomach of pectin-fed rats when compared with control animals. The parietal cells, which showed barely any or no detectable MCT1 in the control group, exhibited a strong intensity of MCT1 on the basolateral membranes in pectin-fed rats. In the small intestine of pectin-fed rats, strong immunopositivity for MCT1 was detected in the brush border and basolateral membranes of the absorptive enterocytes lining the entire villi, while in control rats, weak reactivity was detected on the brush border membrane in a few absorptive enterocytes in the villus tip. In the large intestine of control animals, MCT1 was detected on the basolateral membranes of the epithelia lining the caecum and colon. This staining intensity was markedly increased in pectin-fed rats, along with the appearance of strong reactivity for MCT1 on the apical membranes of the surface and crypt epithelia of caecum and colon. Our results also showed that MCT1 co-localizes with its chaperone, basigin (CD147), in the rat gastrointestinal tract, and that the pectin feeding increased the expression of CD147. In vivo functional studies revealed an enhanced acetate absorption in the colon of pectin-fed in comparison with control animals. We conclude that MCT1 is up-regulated along the gastrointestinal tract of pectin-fed rats, which might represent an adaptive response to the increased availability of its substrates.

A novel nutrient sensing mechanism underlies substrate-induced regulation of monocarboxylate transporter-1

“…We also compared the MCT1 abundance and its apical membrane levels in the colonic tissues of pectin diet or fiber-free diet fed rats, as evaluated by confocal microscopy. Consistent with an earlier report (17), pectin feeding in our studies also increased MCT1 (red) abundance as well as its apical membrane levels compared with fiber-free diet (Fig. 5).…”

“…A recent study demonstrated that pectin feeding increases the expression and function of MCT1 in rat small intestine and colon (17). Furthermore, MCT1 abundance in the apical membranes of enterocytes and colonocytes increased substantially in pectin-fed rats, while in control rats MCT1 was predominantly localized to the basolateral membranes.…”

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

“…On the basis of immunostaining results for MCT in mans (44, 123), pigs (123), and rats (145) (for reviews, 22, 50). In contrast, our (66) and other immunostaining studies (78,128) confirmed the basolateral localization of MCT1 in the epithelial cells of the mouse, rat, dog, bovine and human intestine (Fig. 2a).…”

Effects of Monocarboxylate Transporter Inhibition on the Oral Toxicokinetics/Toxicodynamics of γ-Hydroxybutyrate and γ-Butyrolactone

“…Our in vitro studies in Caco-2 cells also indicate saturable transport of GHB, which is pH dependent and could be inhibited by MCT inhibitors (Lam et al, 2010). These studies suggest that, along with its concentration-dependent renal reabsorption, the dose-dependent oral absorption of GHB is also due to saturation of MCTs, which are present throughout the intestine in both rats and humans (Kirat et al, 2009;Merezhinskaya and Fishbein, 2009). As a lactone, GBL does not represent an MCT substrate, and as such does not exhibit a similar dose-dependent oral absorption process, but it is rapidly absorbed in rats (Lettieri and Fung, 1978).…”