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 and Jimmy D. Bell
Additional contact information
Gary Frost: Faculty of Medicine, Nutrition and Dietetic Research Group, Endocrinology and Metabolism, Imperial College London, Hammersmith Campus
Michelle L. Sleeth: Faculty of Medicine, Nutrition and Dietetic Research Group, Endocrinology and Metabolism, Imperial College London, Hammersmith Campus
Meliz Sahuri-Arisoylu: Metabolic and Molecular Imaging Group, MRC Clinical Science Centre, Imperial College London
Blanca Lizarbe: Laboratory for Imaging and Spectroscopy by Magnetic Resonance (LISMAR), Instituto de Investigaciones Biomédicas de Madrid ‘Alberto Sols’ C.S.I.C./U.A.M.
Sebastian Cerdan: Laboratory for Imaging and Spectroscopy by Magnetic Resonance (LISMAR), Instituto de Investigaciones Biomédicas de Madrid ‘Alberto Sols’ C.S.I.C./U.A.M.
Leigh Brody: Metabolic and Molecular Imaging Group, MRC Clinical Science Centre, Imperial College London
Jelena Anastasovska: Metabolic and Molecular Imaging Group, MRC Clinical Science Centre, Imperial College London
Samar Ghourab: Metabolic and Molecular Imaging Group, MRC Clinical Science Centre, Imperial College London
Mohammed Hankir: Metabolic and Molecular Imaging Group, MRC Clinical Science Centre, Imperial College London
Shuai Zhang: Cellular Stress Group, MRC Clinical Science Centre, Imperial College London
David Carling: Cellular Stress Group, MRC Clinical Science Centre, Imperial College London
Jonathan R. Swann: Food Microbial Sciences Unit, University of Reading
Glenn Gibson: Food Microbial Sciences Unit, University of Reading
Alexander Viardot: Faculty of Medicine, Nutrition and Dietetic Research Group, Endocrinology and Metabolism, Imperial College London, Hammersmith Campus
Douglas Morrison: Stable Isotope Biochemistry Laboratory, Scottish Universities Environmental Research Centre, Rankine Avenue
E Louise Thomas: Metabolic and Molecular Imaging Group, MRC Clinical Science Centre, Imperial College London
Jimmy D. Bell: Metabolic and Molecular Imaging Group, MRC Clinical Science Centre, Imperial College London

Nature Communications, 2014, vol. 5, issue 1, 1-11

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms4611

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