The Warburg effect is ameliorated by culturing transformed cells in the presence of galactose instead of glucose as the primary carbon source. However, metabolic consequences that are in addition to sensitizing the cells to mitochondrial toxins may occur. As such, the screening of pharmaceutical agents against transformed cells while using galactose must be carefully evaluated. Pioglitazone is used in clinical applications to treat type-2 diabetes, but clearly has other off target effects. Human hepatocellular carcinoma cells (HepG2) were cultured in glucose or galactosecontaining medium to investigate the role of pioglitazone on cellular bioenergetics employing calorimetry and respirometry. Compared to cells cultured in 10 mM glucose, HepG2 cells cultured in the presence of 10 mM galactose showed decreased metabolic activity as measured by cellular heat flow. Interestingly, cellular heat flow increased after addition of pioglitazone for cells cultured in glucose, but not for cells cultured in galactose. Our calorimetric data indicate that a reduction in cellular capacity for glycolysis might be the mechanism responsible for the increase in sensitivity to pioglitazone, and likely mitochondrial toxins in general, for cells cultured in galactose. Furthermore, oxygen consumption rates were decreased after addition of pioglitazone to cells grown in glucose, but remained unchanged for cells grown in presence of galactose. Taken together, we demonstrate that pioglitazone induced a reduction in mitochondrial activity that was partially compensated via an increase in glycolysis in the presence of glucose.
Original Publication Information
Grimm, D., et al. "Modulation of Cellular Energetics by Galactose and Pioglitazone." 2017. Cell and Tissue Research 369(3): 641-646.
Grimm, David; Altamirano, Leonardo; Paudel, Sudip; Welker, Leah; Konkle, Mary E.; Chakraborty, Nilay; and Menze, Michael, "Modulation of cellular energetics by galactose and pioglitazone." (2017). Faculty Scholarship. 335.