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The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism

Title: The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism
Authors: Frost, G
Sleeth, ML
Sahuri-Arisoylu, M
Lizarbe, B
Cerdan, S
Brody, L
Anastasovska, J
Ghourab, S
Hankir, M
Zhang, S
Carling, D
Swann, JR
Gibson, G
Viardot, A
Morrison, D
Thomas, EL
Bell, JD
Item Type: Journal Article
Abstract: Increased intake of dietary carbohydrate that is fermented in the colon by the microbiota has been reported to decrease body weight, although the mechanism remains unclear. Here we use in vivo11C-acetate and PET-CT scanning to show that colonic acetate crosses the blood–brain barrier and is taken up by the brain. Intraperitoneal acetate results in appetite suppression and hypothalamic neuronal activation patterning. We also show that acetate administration is associated with activation of acetyl-CoA carboxylase and changes in the expression profiles of regulatory neuropeptides that favour appetite suppression. Furthermore, we demonstrate through 13C high-resolution magic-angle-spinning that 13C acetate from fermentation of 13C-labelled carbohydrate in the colon increases hypothalamic 13C acetate above baseline levels. Hypothalamic 13C acetate regionally increases the 13C labelling of the glutamate–glutamine and GABA neuroglial cycles, with hypothalamic 13C lactate reaching higher levels than the ‘remaining brain’. These observations suggest that acetate has a direct role in central appetite regulation.
Issue Date: 29-Apr-2014
Date of Acceptance: 11-Mar-2014
URI: http://hdl.handle.net/10044/1/40019
DOI: http://dx.doi.org/10.1038/ncomms4611
ISSN: 2041-1723
Publisher: Nature Publishing Group
Journal / Book Title: Nature Communications
Volume: 5
Copyright Statement: This work is licensed under a Creative Commons Attribution 3.0 Unported License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/
Sponsor/Funder: Biotechnology and Biological Sciences Research Council (BBSRC)
Funder's Grant Number: BB/H004971/1
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
MULTIDISCIPLINARY SCIENCES
DIETARY RESISTANT STARCH
GLUCAGON-LIKE PEPTIDE-1
PERIPHERAL INJECTION
NEURONAL ACTIVATION
GLUTAMATE RELEASE
METABOLISM
RECEPTOR
BRAIN
MICE
HYPOTHALAMUS
Acetates
Animals
Appetite
Brain
Carbon Isotopes
Catalysis
Eating
Homeostasis
Hypothalamus
Lactic Acid
Mice
Mice, Inbred C57BL
MD Multidisciplinary
Publication Status: Published
Article Number: 3611
Appears in Collections:Division of Surgery
Clinical Sciences
Molecular Sciences
Department of Medicine
Faculty of Medicine



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