The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism
The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism
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 vivo(11)C-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 (13)C high-resolution magic-angle-spinning that (13)C acetate from fermentation of (13)C-labelled carbohydrate in the colon increases hypothalamic (13)C acetate above baseline levels. Hypothalamic (13)C acetate regionally increases the (13)C labelling of the glutamate-glutamine and GABA neuroglial cycles, with hypothalamic (13)C lactate reaching higher levels than the 'remaining brain'. These observations suggest that acetate has a direct role in central appetite regulation.
Acetates/metabolism, Animals, Appetite, Brain/metabolism, Carbon Isotopes/metabolism, Catalysis, Eating/physiology, Homeostasis/physiology, Hypothalamus/metabolism, Lactic Acid/metabolism, Mice, Mice, Inbred C57BL
1-11
Frost, Gary
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Sleeth, Michelle L
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Sahuri-Arisoylu, Meliz
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Lizarbe, Blanca
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Cerdan, Sebastian
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Brody, Leigh
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Anastasovska, Jelena
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Ghourab, Samar
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Hankir, Mohammed
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Zhang, Shuai
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Carling, David
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Swann, Jonathan R.
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Gibson, Glenn
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Viardot, Alexander
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Morrison, Douglas
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Louise Thomas, E.
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Bell, Jimmy D.
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2014
Frost, Gary
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Sleeth, Michelle L
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Sahuri-Arisoylu, Meliz
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Lizarbe, Blanca
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Cerdan, Sebastian
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Brody, Leigh
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Anastasovska, Jelena
229cc944-5a2e-457c-9297-d020ff9cf682
Ghourab, Samar
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Hankir, Mohammed
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Zhang, Shuai
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Carling, David
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Swann, Jonathan R.
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Gibson, Glenn
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Viardot, Alexander
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Morrison, Douglas
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Louise Thomas, E.
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Bell, Jimmy D.
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Frost, Gary, Sleeth, Michelle L, Sahuri-Arisoylu, Meliz, Lizarbe, Blanca, Cerdan, Sebastian, Brody, Leigh, Anastasovska, Jelena, Ghourab, Samar, Hankir, Mohammed, Zhang, Shuai, Carling, David, Swann, Jonathan R., Gibson, Glenn, Viardot, Alexander, Morrison, Douglas, Louise Thomas, E. and Bell, Jimmy D.
(2014)
The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism.
Nature Communications, 5, , [3611].
(doi:10.1038/ncomms4611).
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 vivo(11)C-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 (13)C high-resolution magic-angle-spinning that (13)C acetate from fermentation of (13)C-labelled carbohydrate in the colon increases hypothalamic (13)C acetate above baseline levels. Hypothalamic (13)C acetate regionally increases the (13)C labelling of the glutamate-glutamine and GABA neuroglial cycles, with hypothalamic (13)C lactate reaching higher levels than the 'remaining brain'. These observations suggest that acetate has a direct role in central appetite regulation.
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ncomms4611
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Accepted/In Press date: 11 March 2014
e-pub ahead of print date: 29 April 2014
Published date: 2014
Keywords:
Acetates/metabolism, Animals, Appetite, Brain/metabolism, Carbon Isotopes/metabolism, Catalysis, Eating/physiology, Homeostasis/physiology, Hypothalamus/metabolism, Lactic Acid/metabolism, Mice, Mice, Inbred C57BL
Identifiers
Local EPrints ID: 441460
URI: http://eprints.soton.ac.uk/id/eprint/441460
ISSN: 2041-1723
PURE UUID: 751dfd99-a6fd-48f8-a992-fc1e79997842
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Date deposited: 12 Jun 2020 16:40
Last modified: 17 Mar 2024 04:00
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Contributors
Author:
Gary Frost
Author:
Michelle L Sleeth
Author:
Meliz Sahuri-Arisoylu
Author:
Blanca Lizarbe
Author:
Sebastian Cerdan
Author:
Leigh Brody
Author:
Jelena Anastasovska
Author:
Samar Ghourab
Author:
Mohammed Hankir
Author:
Shuai Zhang
Author:
David Carling
Author:
Glenn Gibson
Author:
Alexander Viardot
Author:
Douglas Morrison
Author:
E. Louise Thomas
Author:
Jimmy D. Bell
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