ArticleNature medicine2017
Dissociation of muscle insulin sensitivity from exercise endurance in mice by HDAC3 depletion.
Article in Nature medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
71 citing papers in PubMed, 105 citations in OpenAlex.
- Circadian biology and exercise: the time to move.Life metabolism · 2026Review
- Lactylation and lactate: insights into muscle cell epigenetic regulators in exercise.Molecular medicine (Cambridge, Mass.) · 2026Review
- Endometrial NCOR1 deficiency contributes to implantation failure in endometriosis-associated infertility.iScience · 2026Article
- Intermittent AP-1 activation in muscles contributes to exercise-induced health benefits.bioRxiv : the preprint server for biology · 2026Article
- HDAC3-driven immunometabolic reprogramming in type 2 diabetes and its complications: from enzymatic deacetylation to non-enzymatic scaffolding.Frontiers in immunology · 2026Review
- Enhancer regulator MLL4 controls skeletal muscle metabolic efficiency by limiting AMPK-mediated fuel catabolism.Nature communications · 2025Article
- Glucose-Responsive PAGR1-Regulated Skeletal Muscle Gene Program Controls Systemic Glucose Homeostasis and Hepatic Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- Muscle Rev-erb controls time-dependent adaptations to chronic exercise in mice.Nature communications · 2025Article
- Enzyme-independent functions of HDAC3 in the adult heart.Acta pharmaceutica Sinica. B · 2025Article
- Branched-chain amino acid metabolism: Pathophysiological mechanism and therapeutic intervention in metabolic diseases.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025Review
- The biological and immunological significance of the estrogen-related gene IER3 in diabetes.Frontiers in endocrinology · 2025Article
- Role of AMP deaminase in diabetic cardiomyopathy.Molecular and cellular biochemistry · 2024Review
- Proteomic insights into circadian transcription regulation: novel E-box interactors revealed by proximity labeling.Genes & development · 2024Article
- HDAC inhibitors as pharmacological treatment for Duchenne muscular dystrophy: a discovery journey from bench to patients.Trends in molecular medicine · 2024Review
- Biochemical Aspects That Lead to Abusive Use of Trimetazidine in Performance Athletes: A Mini-Review.International journal of molecular sciences · 2024Review
- Resveratrol as a potential protective compound against skeletal muscle insulin resistance.Heliyon · 2023Review
- Epstein-Barr virus-acquired immunodeficiency in myalgic encephalomyelitis-Is it present in long COVID?Journal of translational medicine · 2023Review
- Amino Acid Catabolism: An Overlooked Area of Metabolism.Nutrients · 2023Review
- Daytime-restricted feeding enhances running endurance without prior exercise in mice.Nature metabolism · 2023Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
Abstract
Type 2 diabetes and insulin resistance are associated with reduced glucose utilization in the muscle and poor exercise performance. Here we find that depletion of the epigenome modifier histone deacetylase 3 (HDAC3) specifically in skeletal muscle causes severe systemic insulin resistance in mice but markedly enhances endurance and resistance to muscle fatigue, despite reducing muscle force. This seemingly paradoxical phenotype is due to lower glucose utilization and greater lipid oxidation in HDAC3-depleted muscles, a fuel switch caused by the activation of anaplerotic reactions driven by AMP deaminase 3 (Ampd3) and catabolism of branched-chain amino acids. These findings highlight the pivotal role of amino acid catabolism in muscle fatigue and type 2 diabetes pathogenesis. Further, as genome occupancy of HDAC3 in skeletal muscle is controlled by the circadian clock, these results delineate an epigenomic regulatory mechanism through which the circadian clock governs skeletal muscle bioenergetics. These findings suggest that physical exercise at certain times of the day or pharmacological targeting of HDAC3 could potentially be harnessed to alter systemic fuel metabolism and exercise performance.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.