title: Hypothalamic sensing of ketone bodies after prolonged cerebral exposure leads to metabolic control dysregulation.
abstract: Ketone bodies have been shown to transiently stimulate food intake and modify energy homeostasis regulatory systems following cerebral infusion for a moderate period of time (<6 hours). As ketone bodies are usually enhanced during episodes of fasting, this effect might correspond to a physiological regulation. In contrast, ketone bodies levels remain elevated for prolonged periods during obesity, and thus could play an important role in the development of this pathology. In order to understand this transition, ketone bodies were infused through a catheter inserted in the carotid to directly stimulate the brain for a period of 24 hours. Food ingested and blood circulating parameters involved in metabolic control as well as glucose homeostasis were determined. Results show that ketone bodies infusion for 24 hours increased food intake associated with a stimulation of hypothalamic orexigenic neuropeptides. Moreover, insulinemia was increased and caused a decrease in glucose production despite an increased resistance to insulin. The present study confirms that ketone bodies reaching the brain stimulates food intake. Moreover, we provide evidence that a prolonged hyperketonemia leads to a dysregulation of energy homeostasis control mechanisms. Finally, this study shows that brain exposure to ketone bodies alters insulin signaling and consequently glucose homeostasis.
authors.affiliation: Department of Physiology, University of Lausanne, 1005 Lausanne, Switzerland.
authors.forename: Lionel
authors.initials: L
authors.lastname: Carneiro
authors.affiliation: Department of Physiology, University of Lausanne, 1005 Lausanne, Switzerland.
authors.forename: Sarah
authors.initials: S
authors.lastname: Geller
authors.affiliation: Department of Physiology, University of Lausanne, 1005 Lausanne, Switzerland.
authors.forename: Audrey
authors.initials: A
authors.lastname: Hébert
authors.affiliation: Department of Physiology, University of Lausanne, 1005 Lausanne, Switzerland.
authors.forename: Cendrine
authors.initials: C
authors.lastname: Repond
authors.affiliation: UMR CNRS 6265-INRA 1324-Univ. Bourgogne Franche-Comté Centre des sciences du goût et de l'alimentation, 21000 Dijon, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Fioramonti
authors.affiliation: UMR CNRS 6265-INRA 1324-Univ. Bourgogne Franche-Comté Centre des sciences du goût et de l'alimentation, 21000 Dijon, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Leloup
authors.affiliation: Department of Physiology, University of Lausanne, 1005 Lausanne, Switzerland.
authors.forename: Luc
authors.initials: L
authors.lastname: Pellerin
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000494:pharmacology; D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D002339:Carotid Arteries; D004435:Eating / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D006706:Homeostasis; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D007261:Infusions, Intra-Arterial; D007333:Insulin Resistance; D007657:Ketone Bodies / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008810:Mice, Inbred C57BL; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D027981:Symporters / Q000378:metabolism; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D020155:3-Hydroxybutyric Acid; D055372:AMP-Activated Protein Kinases; D007657:Ketone Bodies; D027501:Monocarboxylic Acid Transporters; D009419:Nerve Tissue Proteins; D019764:Phosphoenolpyruvate Carboxykinase (ATP); D011333:Pro-Opiomelanocortin; D027981:Symporters; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D000099233:Monocarboxylate Transport Protein 1; C490426:Slc16a7 protein, mouse