title: Cerebral activation by fasting induces lactate accumulation in the hypothalamus.
abstract: Carbon-13 ((13)C) high-resolution magic angle spinning (HR-MAS) spectroscopy was used to investigate the neuroglial coupling mechanisms underlying appetite regulation in the brain of C57BL/6J mice metabolizing [1-(13)C]glucose. Control fed or overnight fasted mice received [1-(13)C]glucose (20 micromol/g intraperitoneally [i.p.]), 15 min prior to brain fixation by focused microwaves. The hypothalamic region was dissected from the rest of the brain and (13)C HR-MAS spectra were obtained from both biopsies. Fasting resulted in a significant increase in hypothalamic [3-(13)C]lactate and [2-(13)C]gamma-aminobutyric acid (GABA) relative to the remaining brain. Administration of the orexigenic peptide ghrelin (0.3 nmol/g i.p.) did not increase hypothalamic [3-(13)C]lactate or [2-(13)C]GABA, suggesting that ghrelin signaling is not sufficient to elicit all the metabolic consequences of hypothalamic activation by fasting. Our results indicate that the hypothalamic regulation of appetite involves, in addition to the well-known neuropeptide signaling, increased neuroglial lactate shuttling and augmented GABA concentrations.
authors.affiliation: Laboratory for Imaging and Spectroscopy Magnetic Resonance (LISMAR), Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas (CSIC)/Universidad Autónoma de Madrid (UAM), Madrid, Spain.
authors.forename: Inês R
authors.initials: IR
authors.lastname: Violante
authors.forename: Jelena
authors.initials: J
authors.lastname: Anastasovska
authors.forename: Gina J
authors.initials: GJ
authors.lastname: Sanchez-Canon
authors.forename: Tiago B
authors.initials: TB
authors.lastname: Rodrigues
authors.forename: Valeria
authors.initials: V
authors.lastname: Righi
authors.forename: Laura
authors.initials: L
authors.lastname: Nieto-Charques
authors.forename: James R C
authors.initials: JR
authors.lastname: Parkinson
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Bloom
authors.forename: Jimmy D
authors.initials: JD
authors.lastname: Bell
authors.forename: Sebastián
authors.initials: S
authors.lastname: Cerdán
mesh_terms: D000818:Animals; D002247:Carbon Isotopes / Q000032:analysis; D005215:Fasting / Q000502:physiology*; D007031:Hypothalamus / Q000378:metabolism*; D019344:Lactic Acid / Q000032:analysis*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D002247:Carbon Isotopes; D019344:Lactic Acid