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Cell Metab. 2017 Sep 5;26(3):523-538.e5. doi: 10.1016/j.cmet.2017.08.015.

Distinct Circadian Signatures in Liver and Gut Clocks Revealed by Ketogenic Diet.

Author information

1
Center for Epigenetics and Metabolism, Department of Biological Chemistry, U1233 INSERM, University of California, Irvine, Irvine, CA, USA.
2
Institute for Genomics and Bioinformatics, School of Information and Computer Sciences, University of California, Irvine, Irvine, CA, USA.
3
Center for Epigenetics and Metabolism, Department of Biological Chemistry, U1233 INSERM, University of California, Irvine, Irvine, CA, USA; Center for Metabolic and Degenerative Diseases, Institute of Molecular Medicine, University of Texas Health Sciences Center, Houston, TX, USA.
4
Gladstone Institutes, University of California, San Francisco, 1650 Owens Street, San Francisco, CA 94158, USA.
5
Center for Epigenetics and Metabolism, Department of Biological Chemistry, U1233 INSERM, University of California, Irvine, Irvine, CA, USA. Electronic address: psc@uci.edu.

Abstract

The circadian clock orchestrates rhythms in physiology and behavior, allowing organismal adaptation to daily environmental changes. While food intake profoundly influences diurnal rhythms in the liver, how nutritional challenges are differentially interpreted by distinct tissue-specific clocks remains poorly explored. Ketogenic diet (KD) is considered to have metabolic and therapeutic value, though its impact on circadian homeostasis is virtually unknown. We show that KD has profound and differential effects on liver and intestine clocks. Specifically, the amplitude of clock-controlled genes and BMAL1 chromatin recruitment are drastically altered by KD in the liver, but not in the intestine. KD induces nuclear accumulation of PPARα in both tissues but with different circadian phase. Also, gut and liver clocks respond differently to carbohydrate supplementation to KD. Importantly, KD induces serum and intestinal β-hydroxyl-butyrate levels to robustly oscillate in a circadian manner, an event coupled to tissue-specific cyclic histone deacetylase (HDAC) activity and histone acetylation.

KEYWORDS:

PPARα; circadian clock; histone acetylation; intestine; ketogenic diet; liver; β-hydroxyl-butyrate

PMID:
28877456
DOI:
10.1016/j.cmet.2017.08.015
[Indexed for MEDLINE]
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