A Circadian Rhythm Orchestrated By Histone Deacetylase 3 Controls Hepatic Lipid Metabolism

By A. Lebreton, G. Lakisic, Lauriane Fritsch, T. N. Tham, Ana Camejo, Pierre‐Jean Matteï, B. Regnault, M. Nahori, D. Cabanes, A. Gautreau and 3 more. Science, 2011

694 citations recorded by the source corpus.

Circadian control of liver metabolism is mediated by cycles of recruitment of the histone deacetylase HDAC3. Disruption of the circadian clock exacerbates metabolic diseases, including obesity and diabetes. We show that histone deacetylase 3 (HDAC3) recruitment to the genome displays a circadian rhythm in mouse liver. Histone acetylation is inversely related to HDAC3 binding, and this rhythm is lost when HDAC3 is absent. Although amounts of HDAC3 are constant, its genomic recruitment in liver corresponds to the expression pattern of the circadian nuclear receptor Rev-erbα. Rev-erbα colocalizes with HDAC3 near genes regulating lipid metabolism, and deletion of HDAC3 or Rev-erbα in mouse liver causes hepatic steatosis. Thus, genomic recruitment of HDAC3 by Rev-erbα directs a circadian rhythm of histone acetylation and gene expression required for normal hepatic lipid homeostasis.

Subfields: Endocrine and Autonomic Systems, Physiology

View Paper: https://www.semanticscholar.org/paper/d4c4b13502da264b0baa96ecfaa1cc04627c9831

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Endocrine and Autonomic Systems

1. J. Y. Chiang
2. Tiangang Li
3. Charles A. Czeisler
4. Jeanne F. Duffy
5. C. Cajochen

In Physiology

1. J. Y. Chiang
2. Tiangang Li

Citations in the corpus

• Energy Metabolism in the Liver (2014, neutral): “Mice with liver-specific deficiency of molecular clock Rev-erb α / β develop hepatic steatosis (20, 63).”
• Bile Acid Signaling in Metabolic Disease and Drug Therapy (2014, background): “In Rev-erba mice, lipogenesis is stimulated (Feng et al., 2011).”
• Metabolic Consequences in Humans of Prolonged Sleep Restriction Combined with Circadian Disruption (2012, background): “Peripheral metabolism-related oscillators coordinate both metabolic and circadian pathways (39) required for normal hepatic lipid metabolism and homeostasis (40).”
• Time restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high fat diet (2012, neutral): “However, circadian oscillator components and metabolic regulators also control a large number of downstream effectors which do not exhibit any overt rhythms in expression (Cho et al., 2012; Feng et al., 2011; Rey et al., 2011).”