title: Neuroglial metabolic compartmentation underlying leptin deficiency in the obese ob/ob mice as detected by magnetic resonance imaging and spectroscopy methods.
abstract: Manganese-Enhanced Magnetic Resonance Imaging (MEMRI), (1)H and (13)C High-Resolution-Magic Angle Spinning (HR-MAS) Spectroscopy, and genomic approaches were used to compare cerebral activation and neuronal and glial oxidative metabolism in ad libitum fed C57BL6/J leptin-deficient, genetically obese ob/ob mice. T(1)-weighted Magnetic Resonance Images across the hypothalamic Arcuate and the Ventromedial nuclei were acquired kinetically after manganese infusion. Neuroglial compartmentation was investigated in hypothalamic biopsies after intraperitoneal injections of [1-(13)C]glucose or [2-(13)C]acetate. Total RNA was extracted to determine the effects of leptin deficiency in the expression of representative genes coding for regulatory enzymes of hypothalamic energy pathways and glutamatergic neurotransmission. Manganese-Enhanced Magnetic Resonance Imaging revealed enhanced cerebral activation in the hypothalamic Arcuate and Ventromedial nuclei of the ob/ob mice. (13)C HR-MAS analysis showed increased (13)C accumulation in the hypothalamic glutamate and glutamine carbons of ob/ob mice after the administration of [1-(13)C]glucose, a primarily neuronal substrate. Hypothalamic expression of the genes coding for glucokinase, phosphofructokinase, pyruvate dehydrogenase, and glutamine synthase was not significantly altered while pyruvate kinase expression was slightly upregulated. In conclusion, leptin deficiency associated with obesity led to increased cerebral activation in the hypothalamic Arcuate and Ventromedial nuclei, concomitant with significant increases in neuronal oxidative metabolism and glutamatergic neurotransmission.
authors.affiliation: Laboratory for Imaging and Spectroscopy by Magnetic Resonance (LISMAR), Instituto de Investigaciones Biomédicas de Madrid Alberto Sols C.S.I.C./U.A.M., Madrid, Spain.
authors.forename: Teresa C
authors.initials: TC
authors.lastname: Delgado
authors.forename: Inês R
authors.initials: IR
authors.lastname: Violante
authors.forename: Laura
authors.initials: L
authors.lastname: Nieto-Charques
authors.forename: Sebastián
authors.initials: S
authors.lastname: Cerdán
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000235:genetics; D018698:Glutamic Acid / Q000502:physiology; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism; D020738:Leptin / Q000172:deficiency*; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008345:Manganese; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009457:Neuroglia / Q000378:metabolism*; D009478:Neuropeptide Y / Q000378:metabolism; D010084:Oxidation-Reduction; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D009435:Synaptic Transmission / Q000502:physiology; D014697:Ventromedial Hypothalamic Nucleus / Q000166:cytology / Q000378:metabolism
chemical_list: D020738:Leptin; D009478:Neuropeptide Y; D018698:Glutamic Acid; D008345:Manganese; D012313:RNA