A circadian rhythm orchestrated by histone deacetylase 3 controls hepatic lipid metabolism
Open accessAbstract
Circadian control of liver metabolism is mediated by cycles of recruitment of the histone deacetylase HDAC3.
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This binding oscillation governs the switch between lipid and glucose utilization in hepatocytes.
“This binding oscillation governs the switch between lipid and glucose utilization in hepatocytes.”
From Rett syndrome: a neurological disorder with metabolic components (2018) · cites this paper as [177]
The passages labeled Abstract (page not supplied) report that HDAC3 binding oscillates in mouse liver and regulates a daily cycle of lipid synthesis and accumulation. They do not show that this oscillation governs a switch between lipid and glucose utilization in hepatocytes; the mention of glucose metabolism does not establish such a switch. (LLM, conf=0.86)
Experimental — accuracy not yet measuredDuring the fasting cycle, the NCoR1/SMRT-HDAC3 complex maximally occupies hepatocyte chromatin, repressing expression of genes involved in lipid synthesis and sequestration, and during the feeding cycle it releases chromatin, allowing expression of its targeted loci.
“During the fasting cycle, the NCoR1/SMRT-HDAC3 complex maximally occupies hepatocyte chromatin, repressing the expression of genes involved in lipid synthesis and sequestration. However, during the feeding cycle, it releases chromatin, allowing for expression of its targeted loci [177].”
From Rett syndrome: a neurological disorder with metabolic components (2018) · cites this paper as [177]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredLoss of HDAC3 in liver cells leads to metabolic syndrome and FLD.
“its loss in liver cells leads to metabolic syndrome and FLD56,57.”
From A suppressor screen in Mecp2 mutant mice implicates cholesterol metabolism in Rett syndrome (2013) · cites this paper as [57]
The paper reports that deleting HDAC3 in mouse liver caused marked lipid accumulation and a fatty liver phenotype, supporting the FLD portion. It mentions metabolic syndrome as background in relation to night-shift work, but does not report that hepatic HDAC3 loss causes metabolic syndrome. The supplied copy labels the relevant passage “Abstract” and provides no page number. (LLM, conf=0.88)
Experimental — accuracy not yet measuredHDAC3 regulates lipid homeostasis.
“HDAC3 regulates lipid homeostasis”
From A suppressor screen in Mecp2 mutant mice implicates cholesterol metabolism in Rett syndrome (2013) · cites this paper as [57]
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- Authors
- Feng, D., Liu, T., Sun, Z., Bugge, A., Mullican, S. E., Alenghat, T., Liu, X. S., & Lazar, M. A.
- Affiliations
- University of Pennsylvania Health System (US)
- Harvard University (US)
- Corresponding author
- Feng, Dan
- Liu, Tao
- Lazar, Mitchell A.
- Venue
- Science
- Published
- 2011-03-11
- Volume
- 331
- Issue
- 6022
- Pages
- 1315-1319
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3389392
- OpenAlex
- W1998585946
- Cited by
- 701
- References
- 6
- Citations by year
- 2026: 34 · 2025: 24 · 2024: 31 · 2023: 31 · 2022: 37 · 2021: 63 · 2020: 51 · 2019: 45 · 2018: 48 · 2017: 41 · 2016: 50 · 2015: 54 · 2014: 53 · 2013: 56 · 2012: 53
- FWCI
- 28.87
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- National Human Genome Research Institute (HG4069, R01HG004069)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 19525, RC1DK08623, DK43806, R01DK045586, DK 45586, P01DK049210, RC1DK086239, DK 49210, R37DK043806, R01DK043806, P30DK019525)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- HDAC3, circadian clock, hepatic lipid metabolism, NR1D1, histone acetylation, hepatic steatosis, liver, nuclear receptors, gene expression rhythms, obesity, diabetes mellitus
- MeSH terms
- Histone Deacetylase 3, Animals, Binding Sites, Circadian Rhythm, DNA, Fatty Liver, Gene Expression Regulation, Histone Deacetylases, Histones, Homeostasis, Liver, Mice, Inbred C57BL, Molecular Sequence Data, RNA Polymerase II, Up-Regulation, Genome, Mice, Knockout, Chronobiology Disorders, Epigenesis, Genetic, Chromatin Immunoprecipitation, Lipogenesis, Lipid Metabolism, Mice, Nuclear Receptor Subfamily 1, Group D, Member 1, Nuclear Receptor Co-Repressor 1, Circadian Clocks
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