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The intestinal microbiota programs diurnal rhythms in host metabolism through histone deacetylase 3

Zheng Kuang, Yuhao Wang, Yun Li, Cunqi Ye, Kelly A. Ruhn, Cassie L. Behrendt, View ORCID ProfileEric N. Olson, View ORCID ProfileLora V. Hooper
doi: https://doi.org/10.1101/580613
Zheng Kuang
1Department of Immunology, The University of Texas Southwestern Medical Center, Dallas, TX. 75390
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Yuhao Wang
1Department of Immunology, The University of Texas Southwestern Medical Center, Dallas, TX. 75390
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Yun Li
1Department of Immunology, The University of Texas Southwestern Medical Center, Dallas, TX. 75390
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Cunqi Ye
2Department of Biochemistry, The University of Texas Southwestern Medical Center, Dallas, TX. 75390
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Kelly A. Ruhn
1Department of Immunology, The University of Texas Southwestern Medical Center, Dallas, TX. 75390
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Cassie L. Behrendt
1Department of Immunology, The University of Texas Southwestern Medical Center, Dallas, TX. 75390
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Eric N. Olson
3Department of Molecular Biology, The University of Texas Southwestern Medical Center, Dallas, TX. 75390
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  • ORCID record for Eric N. Olson
Lora V. Hooper
1Department of Immunology, The University of Texas Southwestern Medical Center, Dallas, TX. 75390
4The Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center, Dallas, TX. 75390
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  • ORCID record for Lora V. Hooper
  • For correspondence: Lora.Hooper@UTSouthwestern.edu
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Abstract

Circadian rhythmicity is a defining feature of mammalian metabolism that synchronizes metabolic processes to day-night light cycles. Here, we show that the intestinal microbiota programs diurnal metabolic rhythms in the mouse small intestine through histone deacetylase 3 (HDAC3). The microbiota induced expression of intestinal epithelial HDAC3, which was recruited rhythmically to chromatin and produced synchronized diurnal oscillations in histone acetylation, metabolic gene expression, and nutrient uptake. HDAC3 also functioned non-canonically to coactivate estrogen related receptor α (ERRα), inducing microbiota-dependent rhythmic transcription of the lipid transporter gene Cd36 and promoting lipid absorption and diet-and jet lag-induced obesity. Our findings reveal that HDAC3 integrates microbial and circadian cues to regulate diurnal metabolic rhythms, and pinpoint a key mechanism by which the microbiota controls host metabolism.

One sentence summary The intestinal microbiota induces daily metabolic rhythms and controls lipid uptake through the enzyme histone deacetylase 3.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted March 19, 2019.
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The intestinal microbiota programs diurnal rhythms in host metabolism through histone deacetylase 3
Zheng Kuang, Yuhao Wang, Yun Li, Cunqi Ye, Kelly A. Ruhn, Cassie L. Behrendt, Eric N. Olson, Lora V. Hooper
bioRxiv 580613; doi: https://doi.org/10.1101/580613
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The intestinal microbiota programs diurnal rhythms in host metabolism through histone deacetylase 3
Zheng Kuang, Yuhao Wang, Yun Li, Cunqi Ye, Kelly A. Ruhn, Cassie L. Behrendt, Eric N. Olson, Lora V. Hooper
bioRxiv 580613; doi: https://doi.org/10.1101/580613

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