Acetate mediates a microbiome-brain-β-cell axis to promote metabolic syndrome

Rachel J Perry; Liang Peng; Natasha A Barry; Gary W Cline; Dongyan Zhang; Rebecca L Cardone; Kitt Falk Petersen; Richard G Kibbey; Andrew L Goodman; Gerald I. Shulman

doi:10.1038/nature18309

Acetate mediates a microbiome-brain-β-cell axis to promote metabolic syndrome

Rachel J Perry, Liang Peng, Natasha A Barry, Gary W Cline, Dongyan Zhang, Rebecca L Cardone, Kitt Falk Petersen, Richard G Kibbey, Andrew L Goodman, Gerald I. Shulman

532 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Nature
Volume	534
Issue number	7606
Pages (from-to)	213-7
Number of pages	5
ISSN	0028-0836
DOIs	https://doi.org/10.1038/nature18309
Publication status	Published - 8 Jun 2016

Keywords

Acetates
Animals
Brain
Diet, High-Fat
Gastrointestinal Microbiome
Ghrelin
Glucose
Hyperphagia
Insulin
Insulin-Secreting Cells
Metabolic Syndrome X
Obesity
Parasympathetic Nervous System
Rats
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/nature18309

Cite this

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title = "Acetate mediates a microbiome-brain-β-cell axis to promote metabolic syndrome",

abstract = "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.",

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author = "Perry, {Rachel J} and Liang Peng and Barry, {Natasha A} and Cline, {Gary W} and Dongyan Zhang and Cardone, {Rebecca L} and Petersen, {Kitt Falk} and Kibbey, {Richard G} and Goodman, {Andrew L} and Shulman, {Gerald I.}",

year = "2016",

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doi = "10.1038/nature18309",

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T1 - Acetate mediates a microbiome-brain-β-cell axis to promote metabolic syndrome

AU - Perry, Rachel J

AU - Peng, Liang

AU - Barry, Natasha A

AU - Cline, Gary W

AU - Zhang, Dongyan

AU - Cardone, Rebecca L

AU - Petersen, Kitt Falk

AU - Kibbey, Richard G

AU - Goodman, Andrew L

AU - Shulman, Gerald I.

PY - 2016/6/8

Y1 - 2016/6/8

N2 - 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.

AB - 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.

KW - Acetates

KW - Animals

KW - Brain

KW - Diet, High-Fat

KW - Gastrointestinal Microbiome

KW - Ghrelin

KW - Glucose

KW - Hyperphagia

KW - Insulin

KW - Insulin-Secreting Cells

KW - Metabolic Syndrome X

KW - Obesity

KW - Parasympathetic Nervous System

KW - Rats

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/nature18309

DO - 10.1038/nature18309

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C2 - 27279214

SN - 0028-0836

VL - 534

SP - 213

EP - 217

JO - Nature

JF - Nature

IS - 7606

ER -

Acetate mediates a microbiome-brain-β-cell axis to promote metabolic syndrome

Abstract

Keywords

UN SDGs

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