Characterization of Glucose Transporter 6 in Lipopolysaccharide-Induced Bone Marrow-Derived Macrophage Function.

The polarization processes for M1 versus M2 macrophages are quite distinct in the context of changes in cellular metabolism. M1 macrophages are highly glycolytic, whereas M2 macrophages require a more oxidative nutrient metabolism. An important part of M1 polarization involves upregulation of the glucose transporter (GLUT) GLUT1 to facilitate increased glucose uptake and glycolytic metabolism; however, the role of other glucose transporters in this process is largely unknown. In surveying the Functional Annotation of the Mammalian Genome and Gene Expression Omnibus Profiles databases, we discovered that the glucose transporter GLUT6 is highly upregulated in LPS-activated macrophages. In our previous work, we have not detected mouse GLUT6 protein expression in any noncancerous tissue; therefore, in this study, we investigated the expression and significance of GLUT6 in bone marrow-derived macrophages from wild-type and GLUT6 knockout C57BL/6 mice. We show that LPS-induced M1 polarization markedly upregulated GLUT6 protein, whereas naive macrophages and IL-4-induced M2 macrophages do not express GLUT6 protein. However, despite strong upregulation of GLUT6 in M1 macrophages, the absence of GLUT6 did not alter M1 polarization in the context of glucose uptake, glycolytic metabolism, or cytokine production. Collectively, these data show that GLUT6 is dispensable for LPS-induced M1 polarization and function. These findings are important because GLUT6 is an anticancer drug target, and this study suggests that inhibition of GLUT6 may not impart detrimental side effects on macrophage function to interfere with their antitumor properties.

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