Hypothalamic sensing of ketone bodies after prolonged cerebral exposure leads to metabolic control dysregulation.

Details

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State: Public
Version: Final published version
Serval ID
serval:BIB_12FACAF97C22
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Hypothalamic sensing of ketone bodies after prolonged cerebral exposure leads to metabolic control dysregulation.
Journal
Scientific reports
Author(s)
Carneiro L., Geller S., Hébert A., Repond C., Fioramonti X., Leloup C., Pellerin L.
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Publication state
Published
Issued date
06/10/2016
Peer-reviewed
Oui
Volume
6
Pages
34909
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
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.
Keywords
3-Hydroxybutyric Acid/pharmacology, AMP-Activated Protein Kinases/metabolism, Animals, Carotid Arteries, Eating/drug effects, Eating/genetics, Eating/physiology, Gene Expression Regulation, Homeostasis, Hypothalamus/drug effects, Hypothalamus/metabolism, Hypothalamus/physiopathology, Infusions, Intra-Arterial, Insulin Resistance, Ketone Bodies/genetics, Ketone Bodies/metabolism, Ketone Bodies/pharmacology, Liver/drug effects, Liver/enzymology, Mice, Inbred C57BL, Monocarboxylic Acid Transporters/metabolism, Nerve Tissue Proteins/metabolism, Phosphoenolpyruvate Carboxykinase (ATP)/metabolism, Pro-Opiomelanocortin/metabolism, Symporters/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
19/10/2016 13:56
Last modification date
20/08/2019 12:41
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