Carbon-13 (13C) 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 [1-13C]glucose. Control fed or overnight fasted mice received [1-13C]glucose (20 mol/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 13C HR-MAS spectra were obtained from both biopsies. Fasting resulted in a significant increase in hypothalamic [3-13C]lactate and [2-13C]-aminobutyric acid (GABA) relative to the remaining brain. Administration of the orexigenic peptide ghrelin (0.3 nmol/g i.p.) did not increase hypothalamic [3-13C]lactate or [2-13C]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.
I. R. Violante, J. Anastasovska, G. J. Sanchez-Canon, T. B. Rodrigues, V. Righi, L. Nieto-Charques, et al. (2009). Cerebral Activation by Fasting Induces Lactate Accumulation in the Hypothalamus. MAGNETIC RESONANCE IN MEDICINE, 62(2), 279-283 [10.1002/mrm.22010].
Cerebral Activation by Fasting Induces Lactate Accumulation in the Hypothalamus
RIGHI, VALERIA;
2009
Abstract
Carbon-13 (13C) 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 [1-13C]glucose. Control fed or overnight fasted mice received [1-13C]glucose (20 mol/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 13C HR-MAS spectra were obtained from both biopsies. Fasting resulted in a significant increase in hypothalamic [3-13C]lactate and [2-13C]-aminobutyric acid (GABA) relative to the remaining brain. Administration of the orexigenic peptide ghrelin (0.3 nmol/g i.p.) did not increase hypothalamic [3-13C]lactate or [2-13C]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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
