The intestinal microbiota regulates body composition through NFIL3 and the circadian clock

Yuhao Wang; Zheng Kuang; Xiaofei Yu; Kelly A. Ruhn; Masato Kubo; Lora V. Hooper

doi:10.1126/science.aan0677

The intestinal microbiota regulates body composition through NFIL3 and the circadian clock

Yuhao Wang, Zheng Kuang, Xiaofei Yu, Kelly A. Ruhn, Masato Kubo, Lora V. Hooper

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289 Scopus citations

Abstract

The intestinal microbiota has been identified as an environmental factor that markedly affects energy storage and body-fat accumulation in mammals, yet the underlying mechanisms remain unclear. Here we show that the microbiota regulates body composition through the circadian transcription factor NFIL3. Nfil3 transcription oscillates diurnally in intestinal epithelial cells, and the amplitude of the circadian oscillation is controlled by the microbiota through group 3 innate lymphoid cells, STAT3 (signal transducer and activator of transcription 3), and the epithelial cell circadian clock. NFIL3 controls expression of a circadian lipid metabolic program and regulates lipid absorption and export in intestinal epithelial cells. These findings provide mechanistic insight into how the intestinal microbiota regulates body composition and establish NFIL3 as an essential molecular link among the microbiota, the circadian clock, and host metabolism.

Original language	English (US)
Pages (from-to)	912-916
Number of pages	5
Journal	Science
Volume	357
Issue number	6354
DOIs	https://doi.org/10.1126/science.aan0677
State	Published - Sep 1 2017

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title = "The intestinal microbiota regulates body composition through NFIL3 and the circadian clock",

abstract = "The intestinal microbiota has been identified as an environmental factor that markedly affects energy storage and body-fat accumulation in mammals, yet the underlying mechanisms remain unclear. Here we show that the microbiota regulates body composition through the circadian transcription factor NFIL3. Nfil3 transcription oscillates diurnally in intestinal epithelial cells, and the amplitude of the circadian oscillation is controlled by the microbiota through group 3 innate lymphoid cells, STAT3 (signal transducer and activator of transcription 3), and the epithelial cell circadian clock. NFIL3 controls expression of a circadian lipid metabolic program and regulates lipid absorption and export in intestinal epithelial cells. These findings provide mechanistic insight into how the intestinal microbiota regulates body composition and establish NFIL3 as an essential molecular link among the microbiota, the circadian clock, and host metabolism.",

author = "Yuhao Wang and Zheng Kuang and Xiaofei Yu and Ruhn, {Kelly A.} and Masato Kubo and Hooper, {Lora V.}",

note = "Funding Information: We thank C. L. Behrendt-Boyd, T. Leal, and B. Hassell for assistance with mouse experiments and other members of the Hooper laboratory for discussions and critical reading of the manuscript. This work was supported by NIH grant R01 DK070855 (L.V.H.), a Burroughs Wellcome Foundation Investigators in the Pathogenesis of Infectious Diseases Award (L.V.H.), the Welch Foundation (L.V.H.), and the Howard Hughes Medical Institute (L.V.H.). All data and code to understand and assess the conclusions of this research are available in the main text, supplementary materials, and via the Gene Expression Omnibus repository with accession number GSE100339.",

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AU - Ruhn, Kelly A.

AU - Kubo, Masato

AU - Hooper, Lora V.

N1 - Funding Information: We thank C. L. Behrendt-Boyd, T. Leal, and B. Hassell for assistance with mouse experiments and other members of the Hooper laboratory for discussions and critical reading of the manuscript. This work was supported by NIH grant R01 DK070855 (L.V.H.), a Burroughs Wellcome Foundation Investigators in the Pathogenesis of Infectious Diseases Award (L.V.H.), the Welch Foundation (L.V.H.), and the Howard Hughes Medical Institute (L.V.H.). All data and code to understand and assess the conclusions of this research are available in the main text, supplementary materials, and via the Gene Expression Omnibus repository with accession number GSE100339.

PY - 2017/9/1

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N2 - The intestinal microbiota has been identified as an environmental factor that markedly affects energy storage and body-fat accumulation in mammals, yet the underlying mechanisms remain unclear. Here we show that the microbiota regulates body composition through the circadian transcription factor NFIL3. Nfil3 transcription oscillates diurnally in intestinal epithelial cells, and the amplitude of the circadian oscillation is controlled by the microbiota through group 3 innate lymphoid cells, STAT3 (signal transducer and activator of transcription 3), and the epithelial cell circadian clock. NFIL3 controls expression of a circadian lipid metabolic program and regulates lipid absorption and export in intestinal epithelial cells. These findings provide mechanistic insight into how the intestinal microbiota regulates body composition and establish NFIL3 as an essential molecular link among the microbiota, the circadian clock, and host metabolism.

AB - The intestinal microbiota has been identified as an environmental factor that markedly affects energy storage and body-fat accumulation in mammals, yet the underlying mechanisms remain unclear. Here we show that the microbiota regulates body composition through the circadian transcription factor NFIL3. Nfil3 transcription oscillates diurnally in intestinal epithelial cells, and the amplitude of the circadian oscillation is controlled by the microbiota through group 3 innate lymphoid cells, STAT3 (signal transducer and activator of transcription 3), and the epithelial cell circadian clock. NFIL3 controls expression of a circadian lipid metabolic program and regulates lipid absorption and export in intestinal epithelial cells. These findings provide mechanistic insight into how the intestinal microbiota regulates body composition and establish NFIL3 as an essential molecular link among the microbiota, the circadian clock, and host metabolism.

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The intestinal microbiota regulates body composition through NFIL3 and the circadian clock

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