Obesity and type 2 diabetes in rats are associated with altered brain glycogen and amino-acid homeostasis

• Published in: Journal of cerebral blood flow and metabolism Vol. 30; no. 8; pp. 1527 - 1537
• Main Authors: Sickmann, Helle M, Waagepetersen, Helle S, Schousboe, Arne, Benie, Andrew J, Bouman, Stephan D
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01-08-2010; Sage Publications Ltd; Nature Publishing Group
• Subjects: Alanine - metabolism; Amino Acids - metabolism; Animals; Aspartic Acid - metabolism; Blood Glucose - metabolism; Brain - metabolism; Diabetes Mellitus, Type 2 - metabolism; gamma-Aminobutyric Acid - metabolism; Glutamic Acid - metabolism; Glutamine - metabolism; Glycogen - metabolism; Male; Obesity - metabolism; Original; Rats; Rats, Sprague-Dawley; Rats, Zucker; brain metabolism; type 2 diabetes; glycogen; glutamate–glutamine cycle; obesity
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1038/jcbfm.2010.61

Obesity and type 2 diabetes have reached epidemic proportions; however, scarce information about how these metabolic syndromes influence brain energy and neurotransmitter homeostasis exist. The objective of this study was to elucidate how brain glycogen and neurotransmitter homeostasis are affected by these conditions. [1-13C]glucose was administered to Zucker obese (ZO) and Zucker diabetic fatty (ZDF) rats. Sprague–Dawley (SprD), Zucker lean (ZL), and ZDF lean rats were used as controls. Several brain regions were analyzed for glycogen levels along with 13C-labeling and content of glutamate, glutamine, GABA, aspartate, and alanine. Blood glucose concentrations and 13C enrichment were determined. 13C-labeling in glutamate was lower in ZO and ZDF rats in comparison with the controls. The molecular carbon labeling (MCL) ratio between alanine and glutamate was higher in the ZDF rats. The MCL ratios of glutamine and glutamate were decreased in the cerebellum of the ZO and the ZDF rats. Glycogen levels were also lower in this region. These results suggest that the obese and type 2 diabetic models were associated with lower brain glucose metabolism. Glucose metabolism through the TCA cycle was more decreased than glycolytic activity. Furthermore, reduced glutamate–glutamine cycling was also observed in the obese and type 2 diabetic states.