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

Research output: Contribution to journalArticle

31 Scopus citations

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 noncanonically to coactivate estrogen-related receptor a, inducing microbiota-dependent rhythmic transcription of the lipid transporter gene Cd36 and promoting lipid absorption and diet-induced obesity. Our findings reveal that HDAC3 integrates microbial and circadian cues for regulation of diurnal metabolic rhythms and pinpoint a key mechanism by which the microbiota controls host metabolism.

Original languageEnglish (US)
Pages (from-to)1428-1434
Number of pages7
JournalScience
Volume365
Issue number6460
DOIs
StatePublished - Sep 27 2019

ASJC Scopus subject areas

  • General

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