ArticleNature medicine2017
A microRNA screen reveals that elevated hepatic ectodysplasin A expression contributes to obesity-induced insulin resistance in skeletal muscle.
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 31 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
31 citing papers in PubMed, 67 citations in OpenAlex.
- Emerging roles of OSM and EDA2R-NIK signalling in cancer-associated muscle wasting.Journal of muscle research and cell motility · 2026Review
- Using MetaboAnalyst 6.0 for exposomics data analysis-from LC-MS2 spectra processing to dose-response modeling and causal inference.Nature protocols · 2026Review
- Proteomics signature of moderate-to-vigorous physical activity and risk of multimorbidity of cancer and cardiometabolic diseases.Communications medicine · 2026Article
- The emergence of the ectodysplasin pathway.Open life sciences · 2026Article
- Plasma Proteomics Reveals Dysregulated Pathways Across the SpectrumCirculation. Genomic and precision medicine · 2025Article
- High serum EDA concentration is associated with metabolic syndrome and its determinants.Acta diabetologica · 2025Article
- Increased ectodysplasin-A2-receptor EDA2R is a ubiquitous hallmark of aging and mediates parainflammatory responses.Nature communications · 2025Article
- Spatial and Temporal Expression of Ectodysplasin-A Signaling Pathway Members During Mandibular Condylar Development in Postnatal Mice.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2023Article
- Ectodysplasin Signaling through XEDAR Is Required for Mammary Gland Morphogenesis.The Journal of investigative dermatology · 2023Article
- Article
- Mediterranean Diet Improves Plasma Biomarkers Related to Oxidative Stress and Inflammatory Process in Patients with Non-Alcoholic Fatty Liver Disease.Antioxidants (Basel, Switzerland) · 2023Article
- Association between Circulating Ectodysplasin A and Diabetic Kidney Disease.Journal of diabetes research · 2023Article
- The Role of Ectodysplasin A on the Ocular Surface Homeostasis.International journal of molecular sciences · 2022Review
- Ectodysplasin A (EDA) Signaling: From Skin Appendage to Multiple Diseases.International journal of molecular sciences · 2022Review
- Regulatory network and interplay of hepatokines, stellakines, myokines and adipokines in nonalcoholic fatty liver diseases and nonalcoholic steatohepatitis.Frontiers in endocrinology · 2022Review
- Editorial: Management of Diabetes and its Complications: A Focus on Endothelial Dysfunction.Frontiers in endocrinology · 2022Article
- Functional Role of miR-155 in the Pathogenesis of Diabetes Mellitus and Its Complications.Non-coding RNA · 2021Review
- Investigation of candidate genes and mechanisms underlying obesity associated type 2 diabetes mellitus using bioinformatics analysis and screening of small drug molecules.BMC endocrine disorders · 2021Article
- TREM2 sustains macrophage-hepatocyte metabolic coordination in nonalcoholic fatty liver disease and sepsis.The Journal of clinical investigation · 2021Article
- Ectodysplasin A Is Increased in Non-Alcoholic Fatty Liver Disease, But Is Not Associated With Type 2 Diabetes.Frontiers in endocrinology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Over 40% of microRNAs (miRNAs) are located in introns of protein-coding genes, and many of these intronic miRNAs are co-regulated with their host genes. In such cases of co-regulation, the products of host genes and their intronic miRNAs can cooperate to coordinately regulate biologically important pathways. Therefore, we screened intronic miRNAs dysregulated in the livers of mouse models of obesity to identify previously uncharacterized protein-coding host genes that may contribute to the pathogenesis of obesity-associated insulin resistance and type 2 diabetes mellitus. Our approach revealed that expression of both the gene encoding ectodysplasin A (Eda), the causal gene in X-linked hypohidrotic ectodermal dysplasia (XLHED), and its intronic miRNA, miR-676, was increased in the livers of obese mice. Moreover, hepatic EDA expression is increased in obese human subjects and reduced upon weight loss, and its hepatic expression correlates with systemic insulin resistance. We also found that reducing miR-676 expression in db/db mice increases the expression of proteins involved in fatty acid oxidation and reduces the expression of inflammatory signaling components in the liver. Further, we found that Eda expression in mouse liver is controlled via PPARγ and RXR-α, increases in circulation under conditions of obesity, and promotes JNK activation and inhibitory serine phosphorylation of IRS1 in skeletal muscle. In accordance with these findings, gain- and loss-of-function approaches reveal that liver-derived EDA regulates systemic glucose metabolism, suggesting that EDA is a hepatokine that can contribute to impaired skeletal muscle insulin sensitivity in obesity.
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.