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

Gary Frost; Michelle L. Sleeth; Meliz Sahuri-Arisoylu; Blanca Lizarbe; Sebastian Cerdan; Leigh Brody; Jelena Anastasovska; Samar Ghourab; Mohammed Hankir; Shuai Zhang; David Carling; Jonathan R. Swann; Glenn Gibson; Alexander Viardot; Douglas Morrison; E. Louise Thomas; Jimmy D. Bell

doi:10.1038/ncomms4611

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

Gary Frost^*, Michelle L. Sleeth, Meliz Sahuri-Arisoylu, Blanca Lizarbe, Sebastian Cerdan, Leigh Brody, Jelena Anastasovska, Samar Ghourab, Mohammed Hankir, Shuai Zhang, David Carling, Jonathan R. Swann, Glenn Gibson, Alexander Viardot, Douglas Morrison, E. Louise Thomas, Jimmy D. Bell

^*Corresponding author for this work

Orthodontics

Research output: Contribution to journal › Article › peer-review

1305 Citations (Scopus)

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 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.

Original language	English
Article number	3611
Journal	Nature Communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms4611
Publication status	Published - 29 Apr 2014

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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., & Bell, J. D. (2014). The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Nature Communications, 5, Article 3611. https://doi.org/10.1038/ncomms4611

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title = "The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism",

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 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.",

author = "Gary Frost and Sleeth, {Michelle L.} and Meliz Sahuri-Arisoylu and Blanca Lizarbe and Sebastian Cerdan and Leigh Brody and Jelena Anastasovska and Samar Ghourab and Mohammed Hankir and Shuai Zhang and David Carling and Swann, {Jonathan R.} and Glenn Gibson and Alexander Viardot and Douglas Morrison and Thomas, {E. Louise} and Bell, {Jimmy D.}",

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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 2014, 'The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism', Nature Communications, vol. 5, 3611. https://doi.org/10.1038/ncomms4611

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AU - Frost, Gary

AU - Sleeth, Michelle L.

AU - Sahuri-Arisoylu, Meliz

AU - Lizarbe, Blanca

AU - Cerdan, Sebastian

AU - Brody, Leigh

AU - Anastasovska, Jelena

AU - Ghourab, Samar

AU - Hankir, Mohammed

AU - Zhang, Shuai

AU - Carling, David

AU - Swann, Jonathan R.

AU - Gibson, Glenn

AU - Viardot, Alexander

AU - Morrison, Douglas

AU - Thomas, E. Louise

AU - Bell, Jimmy D.

PY - 2014/4/29

Y1 - 2014/4/29

N2 - 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 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.

AB - 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 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.

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

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