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

Nature Communications - Tập 5 Số 1
Gary Frost1, Michelle Sleeth1, Meliz Sahuri-Arisoylu2, Blanca Lizarbe3, Sebastián Cerdán3, Leigh Brody2, Jelena Anastasovska2, Samar Ghourab2, Mohammed K. Hankir2, Shuai Zhang4, David Carling4, Jonathan R. Swann5, Glenn R. Gibson5, Alexander Viardot1, Douglas J. Morrison6, E. Louise Thomas2, Jimmy D. Bell2
1Faculty 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.
2Metabolic and Molecular Imaging Group, MRC Clinical Science Centre, Imperial College London, London, W12 0NN, UK.
3Laboratory 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.
4Cellular Stress Group, MRC Clinical Science Centre, Imperial College London, London W12 0NN, UK.
5Food Microbial Sciences Unit, Department of Food and Nutritional Sciences, University of Reading, Reading RG6 6AP, UK
6Stable Isotope Biochemistry Laboratory, Scottish Universities Environmental Research Centre, Rankine Avenue, Glasgow G75 0QF, UK.

Tóm tắt

AbstractIncreased 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.

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