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.
Faculty of Medicine, Nutrition and Dietetic Research Group, Division of Diabetes, Endocrinology and Metabolism, Department of Investigative Medicine, Imperial College London, Hammersmith Campus, London W12 0NN, UK.
Gary
G
Frost
Faculty of Medicine, Nutrition and Dietetic Research Group, Division of Diabetes, Endocrinology and Metabolism, Department of Investigative Medicine, Imperial College London, Hammersmith Campus, London W12 0NN, UK.
Michelle L
ML
Sleeth
Metabolic and Molecular Imaging Group, MRC Clinical Science Centre, Imperial College London, London W12 0NN, UK.
Meliz
M
Sahuri-Arisoylu
Laboratory for Imaging and Spectroscopy by Magnetic Resonance (LISMAR), Instituto de Investigaciones Biomédicas de Madrid 'Alberto Sols' C.S.I.C./U.A.M., Madrid 28029, Spain.
Blanca
B
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., Madrid 28029, Spain.
Sebastian
S
Cerdan
Metabolic and Molecular Imaging Group, MRC Clinical Science Centre, Imperial College London, London W12 0NN, UK.
Leigh
L
Brody
Metabolic and Molecular Imaging Group, MRC Clinical Science Centre, Imperial College London, London W12 0NN, UK.
Jelena
J
Anastasovska
Metabolic and Molecular Imaging Group, MRC Clinical Science Centre, Imperial College London, London W12 0NN, UK.
Samar
S
Ghourab
Metabolic and Molecular Imaging Group, MRC Clinical Science Centre, Imperial College London, London W12 0NN, UK.
Mohammed
M
Hankir
Cellular Stress Group, MRC Clinical Science Centre, Imperial College London, London W12 0NN, UK.
Shuai
S
Zhang
Cellular Stress Group, MRC Clinical Science Centre, Imperial College London, London W12 0NN, UK.
David
D
Carling
Food Microbial Sciences Unit, Department of Food and Nutritional Sciences, University of Reading, Reading RG6 6AP, UK.
Jonathan R
JR
Swann
Food Microbial Sciences Unit, Department of Food and Nutritional Sciences, University of Reading, Reading RG6 6AP, UK.
Glenn
G
Gibson
Faculty of Medicine, Nutrition and Dietetic Research Group, Division of Diabetes, Endocrinology and Metabolism, Department of Investigative Medicine, Imperial College London, Hammersmith Campus, London W12 0NN, UK.
Alexander
A
Viardot
Stable Isotope Biochemistry Laboratory, Scottish Universities Environmental Research Centre, Rankine Avenue, Glasgow G75 0QF, UK.
Douglas
D
Morrison
Metabolic and Molecular Imaging Group, MRC Clinical Science Centre, Imperial College London, London W12 0NN, UK.
E
E
Louise Thomas
Metabolic and Molecular Imaging Group, MRC Clinical Science Centre, Imperial College London, London W12 0NN, UK.
Jimmy D
JD
Bell
D000085:Acetates / Q000378:metabolism*; D000818:Animals; D001066:Appetite; D001921:Brain / Q000378:metabolism; D002247:Carbon Isotopes / Q000378:metabolism; D002384:Catalysis; D004435:Eating / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D007031:Hypothalamus / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL
D000085:Acetates; D002247:Carbon Isotopes; D019344:Lactic Acid