Revisiting Glycogen Content in the Human Brain

Abstract

Glycogen provides an important glucose reservoir in the brain since the concentration of glucosyl units stored in glycogen is several fold higher than free glucose available in brain tissue. We have previously reported 3–4 µmol/g brain glycogen content using in vivo ¹³C magnetic resonance spectroscopy (MRS) in conjunction with [1-¹³C]glucose administration in healthy humans, while higher levels were reported in the rodent brain. Due to the slow turnover of bulk brain glycogen in humans, complete turnover of the glycogen pool, estimated to take 3–5 days, was not observed in these prior studies. In an attempt to reach complete turnover and thereby steady state ¹³C labeling in glycogen, here we administered [1-¹³C]glucose to healthy volunteers for 80 h. To eliminate any net glycogen synthesis during this period and thereby achieve an accurate estimate of glycogen concentration, volunteers were maintained at euglycemic blood glucose levels during [1-¹³C]glucose administration and ¹³C-glycogen levels in the occipital lobe were measured by ¹³C MRS approximately every 12 h. Finally, we fitted the data with a biophysical model that was recently developed to take into account the tiered structure of the glycogen molecule and additionally incorporated blood glucose levels and isotopic enrichments as input function in the model. We obtained excellent fits of the model to the ¹³C-glycogen data, and glycogen content in the healthy human brain tissue was found to be 7.8 ± 0.3 µmol/g, a value substantially higher than previous estimates of glycogen content in the human brain.