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Energy balance impairment in mice with Central Nervous System specific glutamate dehydrogenase knockout
Author(s) -
Frigerio Francesca,
Carobbio Stefania,
Gruetter Rolf,
Maechler Pierre
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1042
Subject(s) - glutamate dehydrogenase , medicine , endocrinology , central nervous system , glutamine , glutamate receptor , biology , glutamine synthetase , metabolism , isocitrate dehydrogenase , chemistry , biochemistry , enzyme , amino acid , receptor
Glutamate dehydrogenase (GDH) is a mitochondrial enzyme that plays a major role in glial cells by converting glutamate into alpha‐ketoglutarate, thereby providing energy to the cell. In order to challenge GDH importance in the central nervous system (CNS), we generated CNS specific KO mice, crossing GDH‐exon 7 floxed mice with Nestin‐Cre mice. Homozygous CNS‐specific GDH KO mice were viable and fertile. The KO mice exhibited lower body weight compared to floxed controls. Body weight reduction was not observed in new born pups, suggesting impairment in post‐natal growth and energy utilization. Food intake and energy consumption measured in these mice revealed no difference between KO and controls. At the tissue level, epididymal fat was 30% larger compared to controls, while kidneys and pancreas were smaller. DEXA‐scan measurements confirmed the elevated body fat composition (+23%) observed in CNS‐GDH KO. Investigating whole body energy metabolism, we observed lower plasma insulin concentrations together with glucose intolerance. NMR spectroscopy performed on anesthetized animals indicated elevated levels of glutamate and glutamine in the brain of KO mice versus controls. In conclusion, the absence of GDH in the CNS modified whole body energy balance and storage. We hypothesize that impaired CNS glutamate metabolism affected energetic fluxes in the brain, with outcomes on whole body energy metabolism.