Significance of Short Chain Fatty Acid Transport by Members of the Monocarboxylate Transporter Family (MCT)

Moschen, I.; Bröer, Angelika; Galić, Sandra; Läng, Florian; Bröer, Stefan

doi:10.1007/s11064-012-0857-3

Cited by 66 publications

(48 citation statements)

References 33 publications

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“…Here, we observed that acetate induces expression of both MCT1 and MCT4 over time, without changes in the levels of GLUT1, the main glucose transporter expressed in CRC [16, 41, 47]. Furthermore, upon acetate treatment, we observed an increase in glucose consumption and lactate production up to 24h in CRC cells, which goes in line with the increased expression of MCTs and the need to export the produced lactate [48–51]. Our findings are in agreement with Matthews et al , describing that butyrate and propionate, alone or in combination, significantly increased glucose consumption.…”

Section: Discussionmentioning

confidence: 52%

Characterization of acetate transport in colorectal cancer cells and potential therapeutic implications

et al. 2016

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Acetate, together with other short chain fatty acids has been implicated in colorectal cancer (CRC) prevention/therapy. Acetate was shown to induce apoptosis in CRC cells. The precise mechanism underlying acetate transport across CRC cells membrane, that may be implicated in its selectivity towards CRC cells, is not fully understood and was addressed here. We also assessed the effect of acetate in CRC glycolytic metabolism and explored its use in combination with the glycolytic inhibitor 3-bromopyruvate (3BP). We provide evidence that acetate enters CRC cells by the secondary active transporters MCT1 and/or MCT2 and SMCT1 as well as by facilitated diffusion via aquaporins. CRC cell exposure to acetate upregulates the expression of MCT1, MCT4 and CD147, while promoting MCT1 plasma membrane localization. We also observed that acetate increases CRC cell glycolytic phenotype and that acetate-induced apoptosis and anti-proliferative effect was potentiated by 3BP. Our data suggest that acetate selectivity towards CRC cells might be explained by the fact that aquaporins and MCTs are found overexpressed in CRC clinical cases. Our work highlights the importance that acetate transport regulation has in the use of drugs such as 3BP as a new therapeutic strategy for CRC.

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Section: Discussionmentioning

confidence: 52%

Characterization of acetate transport in colorectal cancer cells and potential therapeutic implications

et al. 2016

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“…27 SCFA can be absorbed through the apical membrane of colonic epithelial cells via four putative mechanisms: non-ionic diffusion of protonated SCFA; 40 exchange with bicarb onate in a ratio of 1:1; 41 via the hydrogen-coupled monocarboxylate transporter 1 (MCT 1), MCT 2 and MCT 4; 42,43 and via sodium-coupled monocarboxylate transporter 1. 43 SCFA absorbed in the caecum, ascending colon or transverse colon are transported into the superior mesenteric vein, whilst SCFA absorbed in the descending colon and sigmoid enter the inferior mesenteric vein, which both drain into the portal vein and liver. 44,45 Interestingly, SCFA absorbed in the sigmoid and rectal region can also bypass the liver via the pelvic plexus, which drains into the inferior vena cava, thereby reaching the systemic circulation directly.…”

Section: Scfa Absorption and Systemic Concentrationsmentioning

confidence: 99%

Short-chain fatty acids in control of body weight and insulin sensitivity

2015

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The connection between the gut microbiota and the aetiology of obesity and cardiometabolic disorders is increasingly being recognized by clinicians. Our gut microbiota might affect the cardiometabolic phenotype by fermenting indigestible dietary components and thereby producing short-chain fatty acids (SCFA). These SCFA are not only of importance in gut health and as signalling molecules, but might also enter the systemic circulation and directly affect metabolism or the function of peripheral tissues. In this Review, we discuss the effects of three SCFA (acetate, propionate and butyrate) on energy homeostasis and metabolism, as well as how these SCFA can beneficially modulate adipose tissue, skeletal muscle and liver tissue function. As a result, these SCFA contribute to improved glucose homeostasis and insulin sensitivity. Furthermore, we also summarize the increasing evidence for a potential role of SCFA as metabolic targets to prevent and counteract obesity and its associated disorders in glucose metabolism and insulin resistance. However, most data are derived from animal and in vitro studies, and consequently the importance of SCFA and differential SCFA availability in human energy and substrate metabolism remains to be fully established. Well-controlled human intervention studies investigating the role of SCFA on cardiometabolic health are, therefore, eagerly awaited.

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“…While other mechanisms are also possible (Dikicioglu et al, 2014), the ABC transporter (Sá-Correia et al, 2009) Pdr18 (Teixeira et al, 2012) and the glyceroaquaporin Fps1 (Teixeira et al, 2009) have properties consistent with such a role as ethanol transporters in yeast, a fact of considerable biotechnological relevance (Dunlop et al, 2011). In the context of biofuels production (and ethanol is a biofuel), and based on similar strategies of toxicity resistance to the one that we exploited earlier (Lanthaler et al, 2011), we now also know them for a variety of other rather lipophilic substances such as alkanes (Tsukagoshi and Aono, 2000; Fernandes et al, 2003; Ankarloo et al, 2010; Chen et al, 2013; Doshi et al, 2013; Foo and Leong, 2013; Ling et al, 2013; Nishida et al, 2013), arenes (Kieboom et al, 1998b), terpenoids (Jasiński et al, 2001; Yazaki, 2006; Foo and Leong, 2013), long-chain fatty acids (Wu et al, 2006a,b; Khnykin et al, 2011; Lin and Khnykin, 2014; Villalba and Alvarez, 2014), short-chain fatty acids (Gimenez et al, 2003; Islam et al, 2008; Moschen et al, 2012; Sá-Pessoa et al, 2013), etc. These are all substances for which bilayer lipoidal diffusion was “once widely assumed” (and presumably still is in some quarters).…”

Section: Intellectual Challenges Around Bilayer Lipoidal Permeabilitymentioning

confidence: 99%

How drugs get into cells: tested and testable predictions to help discriminate between transporter-mediated uptake and lipoidal bilayer diffusion

Kell¹,

Oliver²

2014

Front. Pharmacol.

146

169

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One approach to experimental science involves creating hypotheses, then testing them by varying one or more independent variables, and assessing the effects of this variation on the processes of interest. We use this strategy to compare the intellectual status and available evidence for two models or views of mechanisms of transmembrane drug transport into intact biological cells. One (BDII) asserts that lipoidal phospholipid Bilayer Diffusion Is Important, while a second (PBIN) proposes that in normal intact cells Phospholipid Bilayer diffusion Is Negligible (i.e., may be neglected quantitatively), because evolution selected against it, and with transmembrane drug transport being effected by genetically encoded proteinaceous carriers or pores, whose “natural” biological roles, and substrates are based in intermediary metabolism. Despite a recent review elsewhere, we can find no evidence able to support BDII as we can find no experiments in intact cells in which phospholipid bilayer diffusion was either varied independently or measured directly (although there are many papers where it was inferred by seeing a covariation of other dependent variables). By contrast, we find an abundance of evidence showing cases in which changes in the activities of named and genetically identified transporters led to measurable changes in the rate or extent of drug uptake. PBIN also has considerable predictive power, and accounts readily for the large differences in drug uptake between tissues, cells and species, in accounting for the metabolite-likeness of marketed drugs, in pharmacogenomics, and in providing a straightforward explanation for the late-stage appearance of toxicity and of lack of efficacy during drug discovery programmes despite macroscopically adequate pharmacokinetics. Consequently, the view that Phospholipid Bilayer diffusion Is Negligible (PBIN) provides a starting hypothesis for assessing cellular drug uptake that is much better supported by the available evidence, and is both more productive and more predictive.

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Significance of Short Chain Fatty Acid Transport by Members of the Monocarboxylate Transporter Family (MCT)

Cited by 66 publications

References 33 publications

Characterization of acetate transport in colorectal cancer cells and potential therapeutic implications

Characterization of acetate transport in colorectal cancer cells and potential therapeutic implications

Short-chain fatty acids in control of body weight and insulin sensitivity

How drugs get into cells: tested and testable predictions to help discriminate between transporter-mediated uptake and lipoidal bilayer diffusion

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