title: Evidence for hypothalamic ketone body sensing: impact on food intake and peripheral metabolic responses in mice.
abstract: 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.
authors.affiliation: Department of Physiology, University of Lausanne, Lausanne, Switzerland;
authors.forename: Lionel
authors.initials: L
authors.lastname: Carneiro
authors.affiliation: Department of Physiology, University of Lausanne, Lausanne, Switzerland;
authors.forename: Sarah
authors.initials: S
authors.lastname: Geller
authors.affiliation: Centre National de la Recherche Scientifique, UMR6265, Centre des Sciences du Goût et de l'Alimentation (CSGA), Dijon, France; Institut National de la Recherche Agronomique, UMR1324, CSGA, Dijon, France; and Université de Bourgogne, CSGA, Dijon, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Fioramonti
authors.affiliation: Department of Physiology, University of Lausanne, Lausanne, Switzerland;
authors.forename: Audrey
authors.initials: A
authors.lastname: Hébert
authors.affiliation: Department of Physiology, University of Lausanne, Lausanne, Switzerland;
authors.forename: Cendrine
authors.initials: C
authors.lastname: Repond
authors.affiliation: Centre National de la Recherche Scientifique, UMR6265, Centre des Sciences du Goût et de l'Alimentation (CSGA), Dijon, France; Institut National de la Recherche Agronomique, UMR1324, CSGA, Dijon, France; and Université de Bourgogne, CSGA, Dijon, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Leloup
authors.affiliation: Department of Physiology, University of Lausanne, Lausanne, Switzerland; luc.pellerin@unil.ch.
authors.forename: Luc
authors.initials: L
authors.lastname: Pellerin
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D054369:Agouti-Related Protein / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose; D059305:Diet, High-Fat; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D005943:Gluconeogenesis / Q000187:drug effects / Q000502:physiology; D006706:Homeostasis; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D007657:Ketone Bodies / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009478:Neuropeptide Y / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects
chemical_list: D054369:Agouti-Related Protein; D001786:Blood Glucose; D007657:Ketone Bodies; D009478:Neuropeptide Y; D000263:Adenylate Kinase
keywords: energy homeostasis; glucose homeostasis; monocarboxylate transporters; obesity; β-hydroxybutyrate