Cerebral Activation by Fasting Induces Lactate Accumulation in the Hypothalamus

The hypothalamus is the primary site for appetite regulation and energy homeostasis. Several studies have previously addressed the role of neuropeptide signalling in the control of hypothalamic functions, including the control of feeding fasting cycles. Much less information is available, however, on the action of the amino acid neurotransmitters, glutamate and GABA, and how these could modulate the neuroglial coupling mechanisms underlying neurotransmission events during appetite regulation. On these grounds, methods providing further insight into hypothalamic metabolism and its disturbances entail considerable interest to improve our understanding, prognosis and therapy of the disorders in energy homeostasis and food intake. 13C MRS is an outstanding tool to investigate cerebral metabolism and neuroglial interactions during cerebral activation. Nonetheless, previous in vivo and in vitro 13C MRS studies required either, very large voxel sizes or extracts from large biopsies, precluding accurate cerebral regionalization. Here, we used 13C HR-MAS, an approach requiring very small tissue samples (ca. 10 mg), to study the hypothalamic activation and neuroglial-coupling during a feeding-fasting paradigm and under ghrelin (an orexigenic peptide) administration to mice receiving (1-13C) glucose.