Iron Regulates Cellular Proliferation by Enhancing the Expression of Glucose Transporter GLUT3 in the Liver.

Iron is often accumulated in the liver during pathological conditions such as cirrhosis and cancer. Elevated expression of glucose transporters GLUT1 and GLUT3 is associated with reduced overall survival in patients with hepatocellular carcinoma. However, it is not known whether iron can regulate glucose transporters and contribute to tumor proliferation. In the present study, we found that treatment of human liver cell line HepG2 with ferric ammonium citrate (FAC) resulted in a significant upregulation of GLUT3 mRNA and protein in a dose-dependent manner. Similarly, iron accumulation in mice fed with high dietary iron as well as in mice injected intraperitoneally with iron dextran enhanced the GLUT3 expression drastically in the liver. We demonstrated that iron-induced hepatic GLUT3 upregulation is mediated by the LKB1/AMPK/CREB1 pathway, and this activation was reversed when treated with iron chelator deferiprone. In addition, inhibition of GLUT3 using siRNA prevented iron-mediated increase in the expression of cell cycle markers and cellular hyperproliferation. Furthermore, exogenous sodium beta-hydroxybutyrate treatment prevented iron-mediated hepatic GLUT3 activation both in vitro and in vivo. Together, these results underscore the importance of iron, AMPK, CREB1 and GLUT3 pathways in cell proliferation and highlight the therapeutic potential of sodium beta-hydroxybutyrate in hepatocellular carcinoma with high GLUT3 expression.

The IRONy in Athletic Performance.

Iron is an essential micronutrient for athletes, intricately linked to their performance, by regulating cellular respiration and metabolism. Impaired iron levels in the body can significantly hinder athletic performance. The increased demand for iron due to exercise, coupled with potential dietary iron insufficiencies, particularly among endurance athletes, amplifies the risk of iron deficiency. Moreover, prolonged exercise can impact iron absorption, utilization, storage, and overall iron concentrations in an athlete. On the contrary, iron overload may initially lead to enhanced performance; however, chronic excess iron intake or underlying genetic conditions can lead to detrimental health consequences and may negatively impact athletic performance. Excess iron induces oxidative damage, not only compromising muscle function and recovery, but also affecting various tissues and organs in the body. This narrative review delineates the complex relationship between exercise and iron metabolism, and its profound effects on athletic performance. The article also provides guidance on managing iron intake through dietary adjustments, oral iron supplementation for performance enhancement in cases of deficiency, and strategies for addressing iron overload in athletes. Current research is focused on augmenting iron absorption by standardizing the route of administration while minimizing side effects. Additionally, there is ongoing work to identify inhibitors and activators that affect iron absorption, aiming to optimize the body's iron levels from dietary sources, supplements, and chelators. In summary, by refining the athletic diet, considering the timing and dosage of iron supplements for deficiency, and implementing chelation therapies for iron overload, we can effectively enhance athletic performance and overall well-being.