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

Frost, G. et al. (2014) The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Nature Communications, 5(3611), (doi: 10.1038/ncomms4611)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Morrison, Dr Douglas and Carling, Prof David and Gibson, Prof Glenn
Authors: Frost, G., Sleeth, M. L., Sahuri-Arisoylu, M., Lizarbe, B., Cerdan, S., Brody, L., Anastasovska, J., Ghourab, S., Hankir, M., Zhang, S., Carling, D., Swann, J. R., Gibson, G., Viardot, A., Morrison, D., Thomas, E. L., and Bell, J. D.
College/School:College of Medical Veterinary and Life Sciences > School of Life Sciences
College of Science and Engineering > Scottish Universities Environmental Research Centre
Journal Name:Nature Communications
Publisher:Nature Publishing Group
ISSN:2041-1723
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2014 Macmillan Publishers Limited
First Published:First published in Nature Communications 5:3611
Publisher Policy:Reproduced under a Creative Commons License
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