Monocarboxylate transporter 1 and CD147 are up‐regulated by natural and synthetic peroxisome proliferator‐activated receptor α agonists in livers of rodents and pigs

Abstract

Monocarboxylate transporter (MCT)-1 mediates the transport of ketone bodies and other monocarboxylic acids across the plasma membrane. MCT1 is up-regulated by peroxisome proliferator-activated receptor (PPAR)-alpha, a transcription factor that mediates the adaptive response to fasting by up-regulation of genes involved in fatty acid oxidation and ketogenesis. Here, we show for the first time that MCT1 is up-regulated by dietary natural PPAR-alpha agonists. Both, an oxidized fat and conjugated linoleic acids increased MCT1 mRNA concentration in the liver of rats. Also, in the liver of pigs as non-proliferating species MCT1 was up-regulated upon PPAR-alpha activation by clofibrate, oxidized fat and fasting. Concomitant with up-regulation of MCT1, mRNA level of CD147 was increased in livers of rats and pigs. CD147 is a plasma membrane glycoprotein that is required for translocation and transport activity of MCT1. CD147 mRNA increase upon PPAR-alpha activation could not be observed in mice lacking PPAR-alpha, which also fail in up-regulation of MCT1 indicating a co-regulation of MCT1 and CD147. Analysis of the 5'-flanking region of mouse MCT1 gene by reporter gene assay revealed that promoter activity of mouse MCT1 was not induced by PPAR-alpha, indicating that the 5'-flanking region is not involved in MCT1 regulation by PPAR-alpha.

The mRNA and protein expression of ruminal MCT1 is increased by feeding a mixed hay/concentrate diet compared with hay <i>ad libitum</i> diet (Short Communication)

“…Thus, elevated butyrate concentrations could be a trigger for the upregulation of MCT1 mRNA (1.8-and 2.2-fold in G2 and G3, respectively) and protein expression (1.3-fold) observed in h/c-fed sheep. However, it should be emphasized that besides substrate induction, MCT1 and its chaperon CD147 can be upregulated by nutritiondependent activation of the transcription factor peroxisome proliferator-activated receptor α (PPAR-α) (König et al 2010). The presence and correct conformation of CD147, is essential for correct membrane assembly and functional activity of MCT1 (Kirk et al 2000, Wilson et al 2005.…”

Sequence variations and two levels of MCT1 and CD147 expression in red blood cells and gluteus muscle of horses

“…Parallel expression of MCT1 and CD147 was found in gastric and ovarian cancer cells in studies by Pinheiro et al (2009Pinheiro et al ( , 2010. Moreover the expressions of both MCT1 and CD147 in the liver of rodents and pigs have been shown to be up-regulated by peroxisome proliferator-activated receptor α (PPARα) (König et al, 2010). König et al (2010), however, could not show any direct effect of receptor agonists on the activity of the MCT1 gene.…”

“…Moreover the expressions of both MCT1 and CD147 in the liver of rodents and pigs have been shown to be up-regulated by peroxisome proliferator-activated receptor α (PPARα) (König et al, 2010). König et al (2010), however, could not show any direct effect of receptor agonists on the activity of the MCT1 gene. The association of the low mRNA level with low membrane expression of CD147 and the positive correlation between MCT1 and CD147 mRNA levels are in accordance with the bimodal distribution of MCT1 and CD147 expressions, and suggests that the bimodality is regulated at transcriptional level.…”

Tissue-Specific Expression of Monocarboxylate Transporters during Fasting in Mice

“…The regulation of the thyroid hormone transporters MCT8 and MCT10 remains virtually unknown [29]. Recently, we could demonstrate that MCT1 mRNA is up-regulated by peroxisome proliferator-activated receptor (PPAR)-α in the liver of rats, mice and pigs and also in the rat hepatoma cell line Fao [30], [31]. Increase of MCT1 mRNA in liver, kidney and small intestine upon stimulation of mice with a synthetic PPARα agonist was abolished in mice lacking PPARα (PPARα knockout (KO) mice), although a functional PPAR response element (PPRE) could not be found in the 5′-flanking region of mouse MCT1 gene [30], [31].…”

“…Recently, we could demonstrate that MCT1 mRNA is up-regulated by peroxisome proliferator-activated receptor (PPAR)-α in the liver of rats, mice and pigs and also in the rat hepatoma cell line Fao [30], [31]. Increase of MCT1 mRNA in liver, kidney and small intestine upon stimulation of mice with a synthetic PPARα agonist was abolished in mice lacking PPARα (PPARα knockout (KO) mice), although a functional PPAR response element (PPRE) could not be found in the 5′-flanking region of mouse MCT1 gene [30], [31]. PPARα is a lipid-activated nuclear receptor that acts as a nutritional state sensor in mammalian cells and mediates the adaptive response to fasting by inducing fatty acid oxidation and ketogenesis [32], [33].…”