Evidence for hypothalamic ketone body sensing: impact on food intake and peripheral metabolic responses in mice

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TitreEvidence for hypothalamic ketone body sensing: impact on food intake and peripheral metabolic responses in mice
Type de publicationJournal Article
Year of Publication2016
AuteursCarneiro L, Geller S, Fioramonti X, Hebert A, Repond C, Leloup C, Pellerin L
JournalAMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
Volume310
PaginationE103-E115
Date PublishedJAN 15
Type of ArticleArticle
ISSN0193-1849
Mots-clésbeta-hydroxybutyrate, energy homeostasis, glucose homeostasis, monocarboxylate transporters, Obesity
Résumé

Monocarboxylates have been implicated in the control of energy homeostasis. Among them, the putative role of ketone bodies produced notably during high-fat diet (HFD) has not been thoroughly explored. In this study, we aimed to determine the impact of a specific rise in cerebral ketone bodies on food intake and energy homeostasis regulation. A carotid infusion of ketone bodies was performed on mice to stimulate sensitive brain areas for 6 or 12 h. At each time point, food intake and different markers of energy homeostasis were analyzed to reveal the consequences of cerebral increase in ketone body level detection. First, an increase in food intake appeared over a 12-h period of brain ketone body perfusion. This stimulated food intake was associated with an increased expression of the hypothalamic neuropeptides NPY and AgRP as well as phosphorylated AMPK and is due to ketone bodies sensed by the brain, as blood ketone body levels did not change at that time. In parallel, gluconeogenesis and insulin sensitivity were transiently altered. Indeed, a dysregulation of glucose production and insulin secretion was observed after 6 h of ketone body perfusion, which reversed to normal at 12 h of perfusion. Altogether, these results suggest that an increase in brain ketone body concentration leads to hyperphagia and a transient perturbation of peripheral metabolic homeostasis.

DOI10.1152/ajpendo.00282.2015