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

By G. Frost, M. Sleeth, M. Sahuri-Arisoylu, B. Lizarbe, S. Cerdán, L. Brody, J. Anastasovska, Samar Ghourab, M. Hankir, Shuai Zhang and 7 more. Nature Communications, 2014

1,524 citations recorded by the source corpus.

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. The consumption of fermentable carbohydrates, or fibre, is associated with weight loss. Here the authors show that the metabolite acetate, created by fermentation of fibre in the mouse colon, is taken up into the brain where it induces appetite-suppressing neuronal activity in the hypothalamus.

Subfields: Endocrine and Autonomic Systems, Physiology

View Paper: https://www.semanticscholar.org/paper/3df2406d7633784dee319c6b20b353010a753e3b

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In Physiology

1. J. Cryan
2. Ted G. Dinan
3. G. Clarke
4. E. Canfora
5. M. Collado
6. Ellen E. Blaak
7. Harry Sokol
8. W. Tang

Citations in the corpus

• The Gut-Brain Axis: How Microbiota and Host Inflammasome Influence Brain Physiology and Pathology (2020, background): “Remarkably, ASO-GF mice treated with SCFAs mixture showed again mature microglia, formation of a-syn-aggregates, GI deficits, and significantly impaired performance in several motor tasks, as ASO-SPF mice (103).”
• Dietary Gut Microbial Metabolites, Short-chain Fatty Acids, and Host Metabolic Regulation (2015, background): “Acetate reduces the appetite by changing the expression profiles of appetite regulatory neuropeptides in the hypothalamus through activation of TCA cycle [32].”
• Gut Microbiota in Cardiovascular Health and Disease (2017, background): “In addition, bacterial fermentation of prebiotic soluble fiber generates SCFA, which is thought to exert several beneficial effects including potential amelioration of CVD risk factors.(12,161,162) Given that an alteration in gut microbiota composition has been linked to different diseases, modulati”
• Short chain fatty acids in human gut and metabolic health. (2020, positive): “As previously mentioned, there is also evidence to suggest that large increases in circulating acetate may having a direct effect on the brain leading to a suppression in appetite (Frost et al. , 2014).”
• Regulation of Neurotransmitters by the Gut Microbiota and Effects on Cognition in Neurological Disorders (2021, background): “Notably, gavage administration of 13C-labeled inulin in mice shows that 13C acetate, a metabolite produced by carbohydrate fermentation in the gut, can cross the blood–brain barrier, accumulate mostly in the hypothalamus, and participate in the neuronal–glial cycle of glutamate–glutamine metabolic c”
• SCFA: mechanisms and functional importance in the gut (2020, background): “In the host, SCFA have distinct roles depending of their absorption and local physiologic concentrations((35,36)).”
• Postbiotics—A Step Beyond Pre- and Probiotics (2020, background): “Acetate can also directly regulate appetite in the central nervous system [48], indicating a potential application in preventing cardiovascular diseases.”
• Obesity and type 2 diabetes mellitus: connections in epidemiology, pathogenesis, and treatments (2023, background): “, leptin, PYY, and GLP-1) (55– 57) and activating G protein-coupled receptors (GPCRs) in the brain (58).”
• Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders (2015, background): “Indeed a recent preclinical imaging study demonstrated that microbiota-derived acetate can cross the BBB where it can subsequently alter hypothalamic gene expression (Frost et al., 2014).”
• The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020, background): “Acetate has previously been shown to alter the levels of the neurotransmitters glutamate, glutamine and GABA in the hypothalamus and increase anorexigenic neuropeptide expression (114).”