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

Author

Listed:
  • Rachel J. Perry

    (Yale University School of Medicine)

  • Liang Peng

    (Yale University School of Medicine)

  • Natasha A. Barry

    (Yale University School of Medicine
    Microbial Sciences Institute, Yale University School of Medicine)

  • Gary W. Cline

    (Yale University School of Medicine)

  • Dongyan Zhang

    (Howard Hughes Medical Institute, Yale University School of Medicine)

  • Rebecca L. Cardone

    (Yale University School of Medicine)

  • Kitt Falk Petersen

    (Yale University School of Medicine
    Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen)

  • Richard G. Kibbey

    (Yale University School of Medicine
    Yale University School of Medicine)

  • Andrew L. Goodman

    (Yale University School of Medicine
    Microbial Sciences Institute, Yale University School of Medicine)

  • Gerald I. Shulman

    (Yale University School of Medicine
    Howard Hughes Medical Institute, Yale University School of Medicine
    Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen
    Yale University School of Medicine)

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.

Suggested Citation

  • 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, 2016. "Acetate mediates a microbiome–brain–β-cell axis to promote metabolic syndrome," Nature, Nature, vol. 534(7606), pages 213-217, June.
    • Handle: RePEc:nat:nature:v:534:y:2016:i:7606:d:10.1038_nature18309
    DOI: 10.1038/nature18309
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    Cited by:

    1. Zahraa Al Bander & Marloes Dekker Nitert & Aya Mousa & Negar Naderpoor, 2020. "The Gut Microbiota and Inflammation: An Overview," IJERPH, MDPI, vol. 17(20), pages 1-21, October.
    2. Qi Zhang & Guang Li & Wen Zhao & Xifan Wang & Jingjing He & Limian Zhou & Xiaoxu Zhang & Peng An & Yinghua Liu & Chengying Zhang & Yong Zhang & Simin Liu & Liang Zhao & Rong Liu & Yixuan Li & Wenjian , 2024. "Efficacy of Bifidobacterium animalis subsp. lactis BL-99 in the treatment of functional dyspepsia: a randomized placebo-controlled clinical trial," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    3. Marta G. Novelle, 2021. "Decoding the Role of Gut-Microbiome in the Food Addiction Paradigm," IJERPH, MDPI, vol. 18(13), pages 1-19, June.
    4. Alba Ordoñez-Rodriguez & Pablo Roman & Lola Rueda-Ruzafa & Ana Campos-Rios & Diana Cardona, 2023. "Changes in Gut Microbiota and Multiple Sclerosis: A Systematic Review," IJERPH, MDPI, vol. 20(5), pages 1-16, March.
    5. Gertrude Ecklu-Mensah & Candice Choo-Kang & Maria Gjerstad Maseng & Sonya Donato & Pascal Bovet & Bharathi Viswanathan & Kweku Bedu-Addo & Jacob Plange-Rhule & Prince Oti Boateng & Terrence E. Forrest, 2023. "Gut microbiota and fecal short chain fatty acids differ with adiposity and country of origin: the METS-microbiome study," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    6. Joonatan Palmu & Leo Lahti & Teemu Niiranen, 2021. "Targeting Gut Microbiota to Treat Hypertension: A Systematic Review," IJERPH, MDPI, vol. 18(3), pages 1-14, January.
    7. C. Megan Young & Laurent Beziaud & Pierre Dessen & Angela Madurga Alonso & Albert Santamaria-Martínez & Joerg Huelsken, 2023. "Metabolic dependencies of metastasis-initiating cells in female breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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