Acetate mediates a microbiome-brain-β-cell axis to promote metabolic syndrome.
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.
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Rachel J
RJ
Perry
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Liang
L
Peng
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut 06510, USA.|Microbial Sciences Institute, Yale University School of Medicine, New Haven, Connecticut 06516, USA.
Natasha A
NA
Barry
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Gary W
GW
Cline
Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06519, USA.
Dongyan
D
Zhang
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Rebecca L
RL
Cardone
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.|Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen 2200, Denmark.
Kitt Falk
KF
Petersen
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.|Department of Cellular &Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Richard G
RG
Kibbey
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut 06510, USA.|Microbial Sciences Institute, Yale University School of Medicine, New Haven, Connecticut 06516, USA.
Andrew L
AL
Goodman
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.|Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06519, USA.|Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen 2200, Denmark.|Department of Cellular &Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Gerald I
GI
Shulman
D000085:Acetates / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000502:physiology*; D059305:Diet, High-Fat; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D054439:Ghrelin / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006963:Hyperphagia / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D024821:Metabolic Syndrome / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D010275:Parasympathetic Nervous System / Q000502:physiology; D051381:Rats
D000085:Acetates; D054439:Ghrelin; D007328:Insulin; D005947:Glucose