ArticlePloS one2017
An integrative analysis of tissue-specific transcriptomic and metabolomic responses to short-term dietary methionine restriction in mice.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 48 citations in OpenAlex.
- Dietary sulfur amino acid restriction in humans with overweight and obesity: a translational randomized controlled trial.Journal of translational medicine · 2024Trial
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- Dietary sulfur amino acid restriction improves glucose homeostasis through hepatic de novo serine synthesis.Molecular metabolism · 2026Article
- Methionine restriction improves lipid metabolism disorders and enhances immunity in obese mice through liver lipid remodeling.Frontiers in nutrition · 2026Article
- Dietary sulfur amino acid restriction improves glucose homeostasis through hepaticbioRxiv : the preprint server for biology · 2025Article
- Article
- An Alternative Metabolic Pathway of Glucose Oxidation Induced by Mitochondrial Complex I Inhibition: Serinogenesis and Folate Cycling.International journal of molecular sciences · 2025Article
- Article
- Mitochondrial complex I inhibition triggers NADGeroScience · 2024Article
- Differential effects of bariatric surgery and caloric restriction on hepatic one-carbon and fatty acid metabolism.iScience · 2023Article
- The Origins, Evolution, and Future of Dietary Methionine Restriction.Annual review of nutrition · 2022Review
- Multiomics assessment of dietary protein titration reveals altered hepatic glucose utilization.Cell reports · 2022Article
- Methionine restriction exposes a targetable redox vulnerability of triple-negative breast cancer cells by inducing thioredoxin reductase.Breast cancer research and treatment · 2021Article
- Topology predicts long-term functional outcome in early psychosis.Molecular psychiatry · 2021Article
- The Role of Reduced Methionine in Mediating the Metabolic Responses to Protein Restriction Using Different Sources of Protein.Nutrients · 2021Article
- Regulation of the one carbon folate cycle as a shared metabolic signature of longevity.Nature communications · 2021Article
- HepaticNutrients · 2021Article
- Implementation of dietary methionine restriction using casein after selective, oxidative deletion of methionine.iScience · 2021Article
- The acute transcriptional responses to dietary methionine restriction are triggered by inhibition of ternary complex formation and linked to Erk1/2, mTOR, and ATF4.Scientific reports · 2021Article
- Review
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Dietary methionine restriction (MR) produces a coordinated series of transcriptional responses in peripheral tissues that limit fat accretion, remodel lipid metabolism in liver and adipose tissue, and improve overall insulin sensitivity. Hepatic sensing of reduced methionine leads to induction and release of fibroblast growth factor 21 (FGF21), which acts centrally to increase sympathetic tone and activate thermogenesis in adipose tissue. FGF21 also has direct effects in adipose to enhance glucose uptake and oxidation. However, an understanding of how the liver senses and translates reduced dietary methionine into these transcriptional programs remains elusive. A comprehensive systems biology approach integrating transcriptomic and metabolomic readouts in MR-treated mice confirmed that three interconnected mechanisms (fatty acid transport and oxidation, tricarboxylic acid cycle, and oxidative phosphorylation) were activated in MR-treated inguinal adipose tissue. In contrast, the effects of MR in liver involved up-regulation of anti-oxidant responses driven by the nuclear factor, erythroid 2 like 2 transcription factor, NFE2L2. Metabolomic analysis provided evidence for redox imbalance, stemming from large reductions in the master anti-oxidant molecule glutathione coupled with disproportionate increases in ophthalmate and its precursors, glutamate and 2-aminobutyrate. Thus, cysteine and its downstream product, glutathione, emerge as key early hepatic signaling molecules linking dietary MR to its metabolic phenotype.
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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.