ArticleNature metabolism2022
Independent phenotypic plasticity axes define distinct obesity sub-types.
Article in Nature metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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
27 citing papers in PubMed, 38 citations in OpenAlex.
- Association of Lifestyle-Induced Weight Loss With Gene Expression in Subcutaneous Adipose Tissue in Metabolic Syndrome.Journal of diabetes · 2025Trial
- Beyond Deterministic Fetal Programming: Intrauterine Exposures and the Multifactorial Origins of Adiposity.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2026Review
- Matrix Rigidity Mechanoprimes Microglia for Inflammation Through Cytoskeletal-to-Nuclear Signaling and 3D Spatio-Epigenomic Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Transcriptomic analysis of palmitoylation-related genes reveals a preferential association with BCAA catabolism in adipose tissue from pediatric obesity.Endocrine connections · 2026Article
- Extreme Obesity (BMI ≥ 60 kg/mObesity (Silver Spring, Md.) · 2026Article
- Hyperinsulinaemia as a cause of obesity and cardiometabolic diseases.Nature reviews. Endocrinology · 2026Review
- Chronic High-Fat Diet Does Not Alter Overall Cancer Incidence in Trp53R270H/+ Mice.Cancer research communications · 2026Article
- ADAR1 Controls Macrophage Scavenging and Lipid-Buffering Programs in Metabolic Tissues.European journal of immunology · 2026Article
- Network pharmacology identifies AKR1C3 and KYNU as potential targets of Astragalus Membranaceus and Ephedra in pediatric obesity-associated asthma.Scientific reports · 2025Article
- Metaflammation's Role in Systemic Dysfunction in Obesity: A Comprehensive Review.International journal of molecular sciences · 2025Review
- Gene expression variation across genetically identical individuals predicts reproductive traits.eLife · 2025Article
- Anoikis-Related Genes Impact Prognosis and Tumor Microenvironment in Bladder Cancer.Molecular biotechnology · 2025Article
- BifurcatoR: A Framework for Revealing Clinically Actionable Signal in Variance Masquerading as Noise.bioRxiv : the preprint server for biology · 2025Article
- Epigenetics and individuality: from concepts to causality across timescales.Nature reviews. Genetics · 2025Review
- Optimized RNA sequencing deconvolution illustrates the impact of obesity and weight loss on cell composition of human adipose tissue.Obesity (Silver Spring, Md.) · 2025Article
- An overview of obesity-related complications: The epidemiological evidence linking body weight and other markers of obesity to adverse health outcomes.Diabetes, obesity & metabolism · 2025Review
- Understanding Adipose Tissue Dysfunction.Journal of obesity & metabolic syndrome · 2024Review
- Molecular Mechanisms behind Obesity and Their Potential Exploitation in Current and Future Therapy.International journal of molecular sciences · 2024Review
- Article
- Limited WKY chromosomal regions confer increases in anxiety and fear memory in a F344 congenic rat strain.Physiological genomics · 2024Article
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Authors and funding
25 authors at 13 institutions in 7 countries.
Funding
Abstract
Studies in genetically 'identical' individuals indicate that as much as 50% of complex trait variation cannot be traced to genetics or to the environment. The mechanisms that generate this 'unexplained' phenotypic variation (UPV) remain largely unknown. Here, we identify neuronatin (NNAT) as a conserved factor that buffers against UPV. We find that Nnat deficiency in isogenic mice triggers the emergence of a bi-stable polyphenism, where littermates emerge into adulthood either 'normal' or 'overgrown'. Mechanistically, this is mediated by an insulin-dependent overgrowth that arises from histone deacetylase (HDAC)-dependent β-cell hyperproliferation. A multi-dimensional analysis of monozygotic twin discordance reveals the existence of two patterns of human UPV, one of which (Type B) phenocopies the NNAT-buffered polyphenism identified in mice. Specifically, Type-B monozygotic co-twins exhibit coordinated increases in fat and lean mass across the body; decreased NNAT expression; increased HDAC-responsive gene signatures; and clinical outcomes linked to insulinemia. Critically, the Type-B UPV signature stratifies both childhood and adult cohorts into four metabolic states, including two phenotypically and molecularly distinct types of obesity.
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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 Socratic graph.