Distribution of monocarboxylate transporters MCT1-MCT8 in rat tissues and human skeletal muscle

Abstract

In the past decade, a family of monocarboxylate transporters (MCTs) have been identified that can potentially transport lactate, pyruvate, ketone bodies, and branched-chain ketoacids. Currently, 14 such MCTs are known. However, many orphan transporters exist that have transport capacities that remain to be determined. In addition, the tissue distribution of many of these MCTs is not well defined. Such a cataloging can, at times, begin to suggest the metabolic role of a particular MCT. Recently, a number of antibodies against selected MCTs (MCT1, -2, -4, and -5 to -8) have become commercially available. Therefore, we examined the protein expression of these MCTs in a large number of rat tissues (heart, skeletal muscle, skin, brain, testes, vas deferens, adipose tissue, liver, kidney, spleen, and pancreas), as well as in human skeletal muscle. Unexpectedly, many tissues coexpressed 4-5 MCTs. In particular, in rat skeletal muscle MCT1, MCT2, MCT4, MCT5, and MCT6 were observed. In human muscle, these same MCTs were present. We also observed a pronounced MCT7 signal in human muscle, whereas a very faint signal occurred for MCT8. In rat heart, which is an important metabolic sink for lactate, we confirmed that MCT1 and -2 were expressed. In addition, MCT6 and -8 were also prominently expressed in this tissue, although it is known that MCT8 does not transport aromatic amino acids or lactate. This catalog of MCTs in skeletal muscle and other tissues has revealed an unexpected complexity of coexpression, which makes it difficult to associate changes in monocarboxylate transport with the expression of a particular MCT. The differences in transport kinetics for lactate and pyruvate are only known for MCT1, -2 and -4. Transport kinetics remain to be established for many other MCTs. In conclusion, this study suggests that in skeletal muscle, as well as other tissues, lactate and pyruvate transport rates may not only involve MCT1 and -4, as other monocarboxylate transporters are also expressed in rat (MCT2, -5, -6) and human skeletal muscle (MCT2, -5, -6, -7).

A monocarboxylate transporter required for hepatocyte secretion of ketone bodies during fasting

“…In contrast to the nearly ubiquitous expression of Slc16a1 (MCT1) and Slc16a7 (MCT2), the expression of Slc16a6 is limited to liver, pancreas, skin, vas deferens, and testis of adult rats (Bonen et al 2006). The expression pattern of Slc16a6 during development is not known.…”

Glyceroneogenesis Is the Dominant Pathway for Triglyceride Glycerol Synthesis in Vivo in the Rat

“…It is possible that the glycolytic cells metabolize glucose to lactate, which is then released into the interstitium where it is available as a glyceroneogenic substrate for the triglyceridestoring cells. Adipocytes express the gene for the monocarboxylate transporter-1, which may be responsible for both lactate release, as well as its uptake from the interstitium of adipose tissue (56). In vivo studies in healthy, lean humans using microdialysis techniques show that after an overnight fast the interstitial concentration of lactate is significantly higher in abdominal and femoral subcutaneous adipose tissue than in plasma, suggesting a local release of lactate (57).…”

Regulation of Monocarboxylate Transporter 1 in Skeletal Muscle Cells by Intracellular Signaling Pathways

“…[3][4][5][6][7][8] MCT1 is thought to play an important role in the regulation of L-lactic acid circulation into and out of muscle and the maintenance of homeostasis of skeletal muscle cells. MCT1 has been found in all fiber types in muscle tissue, but it is more abundant in muscles that have a high percentage of oxidative fibers than in glycolytic fibers and thus has been suggested to play a major role in influx of L-lactic acid for oxidation.…”