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

Details

Ressource 1Download: 5_26530151_Postprint.pdf (2138.76 [Ko])
State: Public
Version: Author's accepted manuscript
Serval ID
serval:BIB_43AB02AFD1D6
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Evidence for hypothalamic ketone body sensing: impact on food intake and peripheral metabolic responses in mice.
Journal
American Journal of Physiology. Endocrinology and Metabolism
Author(s)
Carneiro L., Geller S., Fioramonti X., Hébert A., Repond C., Leloup C., Pellerin L.
ISSN
1522-1555 (Electronic)
ISSN-L
0193-1849
Publication state
Published
Issued date
2016
Peer-reviewed
Oui
Volume
310
Number
2
Pages
E103-E115
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
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.
Keywords
Adenylate Kinase/metabolism, Agouti-Related Protein/metabolism, Animals, Blood Glucose, Diet, High-Fat, Eating/drug effects, Eating/physiology, Energy Metabolism/drug effects, Energy Metabolism/physiology, Gluconeogenesis/drug effects, Gluconeogenesis/physiology, Homeostasis, Hypothalamus/drug effects, Hypothalamus/metabolism, Insulin Resistance/physiology, Ketone Bodies/pharmacology, Male, Mice, Mice, Inbred C57BL, Neuropeptide Y/metabolism, Phosphorylation/drug effects
Pubmed
Web of science
Create date
09/11/2015 9:55
Last modification date
20/08/2019 13:47
Usage data