title: 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 (13)C magnetic resonance spectroscopy (MRS) in conjunction with [1-(13)C]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 (13)C labeling in glycogen, here we administered [1-(13)C]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-(13)C]glucose administration and (13)C-glycogen levels in the occipital lobe were measured by (13)C 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 (13)C-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.
authors.affiliation: Department of Radiology, Center for Magnetic Resonance Research, University of Minnesota, 2021 6th St. S.E., Minneapolis, MN, 55455, USA. gulin@cmrr.umn.edu.
authors.forename: Gülin
authors.initials: G
authors.lastname: Öz
authors.affiliation: Museo storico della fisica e Centro di studi e ricerche Enrico Fermi, Rome, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: DiNuzzo
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Anjali
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Amir
authors.initials: A
authors.lastname: Moheet
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Seaquist
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D001923:Brain Chemistry / Q000502:physiology*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism*; D064368:Healthy Volunteers; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008962:Models, Theoretical; D012016:Reference Values
chemical_list: D001786:Blood Glucose; D006003:Glycogen; D005947:Glucose
keywords: 13C magnetic resonance spectroscopy; Glycogen; Human brain; Mathematical modeling