ArticlePloS one2014
Anaplerotic triheptanoin diet enhances mitochondrial substrate use to remodel the metabolome and improve lifespan, motor function, and sociability in MeCP2-null mice.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
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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
39 citing papers in PubMed, 69 citations in OpenAlex.
- The Pharmacokinetics of Triheptanoin and Its Metabolites in Healthy Subjects and Patients With Long-Chain Fatty Acid Oxidation Disorders.Clinical pharmacology in drug development · 2021Trial
- Leptin antagonism improves Rett syndrome phenotype in symptomatic Mecp2-deficient mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- MECP2 Dysfunction in Rett Syndrome: Molecular Mechanisms, Multisystem Pathology, and Emerging Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Rett Syndrome: Thinking Beyond Brain Borders.Advances in experimental medicine and biology · 2025Review
- Comprehensive High-Depth Proteomic Analysis of Plasma Extracellular Vesicles Containing Preparations in Rett Syndrome.Biomedicines · 2024Article
- Diet and Nutrients in Rare Neurological Disorders: Biological, Biochemical, and Pathophysiological Evidence.Nutrients · 2024Review
- Review
- Systemic proteome phenotypes reveal defective metabolic flexibility in Mecp2 mutants.Human molecular genetics · 2023Article
- Mitochondrial modulation with leriglitazone as a potential treatment for Rett syndrome.Journal of translational medicine · 2023Article
- Systemic Proteome Phenotypes Reveal Defective Metabolic Flexibility in Mecp2 Mutants.bioRxiv : the preprint server for biology · 2023Article
- Paving Therapeutic Avenues for FOXG1 Syndrome: Untangling Genotypes and Phenotypes from a Molecular Perspective.International journal of molecular sciences · 2022Review
- Molecular Signatures of Response to Mecasermin in Children With Rett Syndrome.Frontiers in neuroscience · 2022Article
- Article
- Article
- Transcriptomic and Epigenomic Landscape in Rett Syndrome.Biomolecules · 2021Review
- Leptin down-regulates KCC2 activity and controls chloride homeostasis in the neonatal rat hippocampus.Molecular brain · 2020Article
- Triheptanoin: First Approval.Drugs · 2020Review
- Drug Studies on Rett Syndrome: From Bench to Bedside.Journal of autism and developmental disorders · 2020Review
- Determining the Bioenergetic Capacity for Fatty Acid Oxidation in the Mammalian Nervous System.Molecular and cellular biology · 2020Article
- Mitochondrial Damage and Necroptosis in Aging Cochlea.International journal of molecular sciences · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 3 countries.
Funding
Abstract
Rett syndrome (RTT) is an autism spectrum disorder (ASD) caused by mutations in the X-linked MECP2 gene that encodes methyl-CpG binding protein 2 (MeCP2). Symptoms range in severity and include psychomotor disabilities, seizures, ataxia, and intellectual disability. Symptom onset is between 6-18 months of age, a critical period of brain development that is highly energy-dependent. Notably, patients with RTT have evidence of mitochondrial dysfunction, as well as abnormal levels of the adipokines leptin and adiponectin, suggesting overall metabolic imbalance. We hypothesized that one contributor to RTT symptoms is energy deficiency due to defective nutrient substrate utilization by the TCA cycle. This energy deficit would lead to a metabolic imbalance, but would be treatable by providing anaplerotic substrates to the TCA cycle to enhance energy production. We show that dietary therapy with triheptanoin significantly increased longevity and improved motor function and social interaction in male mice hemizygous for Mecp2 knockout. Anaplerotic therapy in Mecp2 knockout mice also improved indicators of impaired substrate utilization, decreased adiposity, increased glucose tolerance and insulin sensitivity, decreased serum leptin and insulin, and improved mitochondrial morphology in skeletal muscle. Untargeted metabolomics of liver and skeletal muscle revealed increases in levels of TCA cycle intermediates with triheptanoin diet, as well as normalizations of glucose and fatty acid biochemical pathways consistent with the improved metabolic phenotype in Mecp2 knockout mice on triheptanoin. These results suggest that an approach using dietary supplementation with anaplerotic substrate is effective in improving symptoms and metabolic health in RTT.
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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.