Acetate mediates a microbiome-brain-β cell axis promoting metabolic syndrome

By R. Perry, Liang Peng, N. Barry, G. Cline, Dongyan Zhang, Rebecca L. Cardone, K. Petersen, R. Kibbey, A. Goodman, Gerald I. Shulman. Nature, 2016

1,123 citations recorded by the source corpus.

Obesity, insulin resistance and the metabolic syndrome are associated with changes to the gut microbiota; however, the mechanism by which modifications to the gut microbiota might lead to these conditions is unknown. Here we show that increased production of acetate by an altered gut microbiota in rodents leads to activation of the parasympathetic nervous system, which, in turn, promotes increased glucose-stimulated insulin secretion, increased ghrelin secretion, hyperphagia, obesity and related sequelae. Together, these findings identify increased acetate production resulting from a nutrient–gut microbiota interaction and subsequent parasympathetic activation as possible therapeutic targets for obesity. Increased acetate production by an altered gut microbiota in rats fed a high-fat diet activates the parasympathetic nervous system, which in turn promotes increased insulin secretion, increased food intake, obesity and related changes. Changes to gut microbiota, and altered faecal short-chain fatty acid concentrations, have been associated with obesity, insulin resistance and the metabolic syndrome, but no causal links have been established. Gerald Shulman and colleagues show that a gut microbiota–nutrient interaction increases acetate production in rodents on a high-fat diet. This leads to activation of the parasympathetic nervous system — the part of the nervous system that controls 'subconscious' operations such as heart rate and digestion — which in turn promotes increased glucose-stimulated insulin secretion, ghrelin secretion, hyperphagia and obesity.

Subfields: Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/b7ee0cca7d6986d2b04193d0e9fb3507bf506a0a

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Citations in the corpus

Gut Microbiota in Cardiovascular Health and Disease (2017, background): “Others have been reported to stimulate the parasympathetic nervous system, thereby impacting glucose homeostasis and other metabolic processes linked to development of metabolic syndrome.(46)”
Short chain fatty acids in human gut and metabolic health. (2020, positive): “However, an investigation by Perry et al. (2016) Although it is the least studied out of the three SCFA in rodents, propionate has shown to directly attenuate high fat diet weight gain in all 4 studies identified with a 10-14 day up to 12 week duration (De Vadder et al. , 2014; Den Besten et al. ,…”
The Controversial Role of Human Gut Lachnospiraceae (2020, background): “The role of acetate in driving obesity depends on the gut microbiota and on dietary fiber intake [84].”
The role of short-chain fatty acids in immunity, inflammation and metabolism (2020, background): “In mice, SCFAs (propionate) can increase intestinal gluconeogenesis through the intestinal-brain pathway mediated by FFAR3, which may be related to increased glucose homeostasis and weight loss (De Vadder et al. 2014; Perry et al. 2016).”
The Gut Microbiota and Inflammation: An Overview (2020, background): “As ghrelin is an appetite-stimulating hormone associated with greater food intake, acetate may consequently be linked with weight gain [86].”
Role of the microbiome in human development (2019, background): “51 Butyrate and acetate regulate satiety, 66 67 with acetate being obesogenic.”
Short‐chain fatty acids: microbial metabolites that alleviate stress‐induced brain–gut axis alterations (2018, background): “It is therefore essential to emphasise that physiologically relevant levels of acetate and propionate have been reported to directly influence the brain (Perry et al. 2016; Hoyles et al. 2018).”
Human gut microbiota/microbiome in health and diseases: a review (2020, background): “The disturbance of the biosynthesis of short chain fatty acids causes many pathological consequences for the host (Perry et al. 2016).”