Non-invasive quantification of brain glycogen absolute concentration

• Published in: Journal of neurochemistry 2008-12, Vol.107 (5), p.1414-1423
• Main Authors: Morgenthaler, Florence D, van Heeswijk, Ruud B, Xin, Lijing, Laus, Sabrina, Frenkel, Hanne, Lei, Hongxia, Gruetter, Rolf
• Format: Article
• Language: English
• Subjects: 13C; Animals; Aspartic Acid - analogs & derivatives; Aspartic Acid - metabolism; Biochemistry; Biochemistry and metabolism; Biological and medical sciences; Brain - metabolism; Brain Chemistry; C; Central nervous system; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Fundamental and applied biological sciences. Psychology; Glucose; Glycogen - metabolism; insulin; Magnetic Resonance Imaging - methods; Magnetic Resonance Spectroscopy - methods; Measurement techniques; Neurology; nuclear magnetic resonance; nuclear magnetic resonance spectroscopy; Rats; Rats, Sprague-Dawley; Rodents; turnover; Vertebrates: nervous system and sense organs
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2008.05717.x

The only currently available method to measure brain glycogen in vivo is ¹³C NMR spectroscopy. Incorporation of ¹³C-labeled glucose (Glc) is necessary to allow glycogen measurement, but might be affected by turnover changes. Our aim was to measure glycogen absolute concentration in the rat brain by eliminating label turnover as variable. The approach is based on establishing an increased, constant ¹³C isotopic enrichment (IE). ¹³C-Glc infusion is then performed at the IE of brain glycogen. As glycogen IE cannot be assessed in vivo, we validated that it can be inferred from that of N-acetyl-aspartate IE in vivo: After [1-¹³C]-Glc ingestion, glycogen IE was 2.2 ± 0.1 fold that of N-acetyl-aspartate (n = 11, R² = 0.77). After subsequent Glc infusion, glycogen IE equaled brain Glc IE (n = 6, paired t-test, p = 0.37), implying isotopic steady-state achievement and complete turnover of the glycogen molecule. Glycogen concentration measured in vivo by ¹³C NMR (mean ± SD: 5.8 ± 0.7 μmol/g) was in excellent agreement with that in vitro (6.4 ± 0.6 μmol/g, n = 5). When insulin was administered, the stability of glycogen concentration was analogous to previous biochemical measurements implying that glycogen turnover is activated by insulin. We conclude that the entire glycogen molecule is turned over and that insulin activates glycogen turnover.