ArticleMolecular metabolism2017
Nrg4 promotes fuel oxidation and a healthy adipokine profile to ameliorate diet-induced metabolic disorders.
Article in Molecular metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 2 of them syntheses that pooled it.
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Who cites it
88 citing papers in PubMed, 2 syntheses or guidelines pooled it, 149 citations in OpenAlex.
- The impact of serum neuregulin 4 (NRG-4) levels on non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis.BMC gastroenterology · 2025Pooled it
- Pooled it
- Trial
- A Feedforward Loop within the Thyroid-Brown Fat Axis Facilitates Thermoregulation.Scientific reports · 2020Trial
- Targeting receptor tyrosine kinases: from molecular mechanisms to clinical therapeutics.Signal transduction and targeted therapy · 2026Review
- Expression and significance of ependymin-related protein 1 and neuregulin 4 in the serum of patients with polycystic ovary syndrome.International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics · 2026Article
- Housing at 27 °C, a Near-Thermoneutral Temperature, Exacerbates Metabolic Dysfunction-Associated Steatohepatitis in C57BL/6J Mice.International journal of molecular sciences · 2026Article
- METTL14 Hinders DCM Progression via Mediating the m6A Methylation of NRG4 in HG-Induced H9C2 Cells.Molecular biotechnology · 2026Article
- Impact of miR-181a-5p and miR-1249-3p treatment on the visceral adipose tissue transcriptome of female mice.GeroScience · 2026Article
- Homoharringtonine exhibits senotherapeutic activity that mitigates diet- and age-associated obesity and insulin resistance and extends lifespan in mice.Nature communications · 2026Article
- Itaconate Promotes Cold Adaptation and Myocardial Protection by Enhancing Brown Adipose Tissue Metabolism.Metabolites · 2026Article
- Neuregulin 4 in Insulin Resistance: Mechanisms, Controversies, and Therapeutic Perspectives.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- Thermogenic adipose tissue in older adults with obesity: a narrative review of mechanisms, brown fat resistance, and the translational relevance of exercise and nutrition.Frontiers in nutrition · 2026Review
- Article
- The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction: A Novel Framework to Explain Pathogenesis and Guide Treatment.Journal of the American College of Cardiology · 2025Review
- Thermoneutral housing worsens MASLD and reveals defective brown adipose tissue response to β3-adrenergic stimulation.iScience · 2025Article
- Secreted proteins in treating metabolic dysfunction-associated steatotic liver disease: from bench towards bedside.Protein & cell · 2025Review
- Inflammation in MASLD progression and cancer.JHEP reports : innovation in hepatology · 2025Review
- Lifestyle Interventions to Tackle Cardiovascular Risk in Thyroid Hormone Signaling Disorders.Nutrients · 2025Review
- Adipokines and Adipose Tissue: The Role and Use of Sodium-Glucose Co-Transporter-2 (SGLT-2) Inhibitors in Patients with Diabetes or Heart Failure.Biomedicines · 2025Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
objectiveBrown and white adipose tissue exerts pleiotropic effects on systemic energy metabolism in part by releasing endocrine factors. Neuregulin 4 (Nrg4) was recently identified as a brown fat-enriched secreted factor that ameliorates diet-induced metabolic disorders, including insulin resistance and hepatic steatosis. However, the physiological mechanisms through which Nrg4 regulates energy balance and glucose and lipid metabolism remain incompletely understood. The aims of the current study were: i) to investigate the regulation of adipose Nrg4 expression during obesity and the physiological signals involved, ii) to elucidate the mechanisms underlying Nrg4 regulation of energy balance and glucose and lipid metabolism, and iii) to explore whether Nrg4 regulates adipose tissue secretome gene expression and adipokine secretion.
methodsWe examined the correlation of adipose Nrg4 expression with obesity in a cohort of diet-induced obese mice and investigated the upstream signals that regulate Nrg4 expression. We performed metabolic cage and hyperinsulinemic-euglycemic clamp studies in Nrg4 transgenic mice to dissect the metabolic pathways regulated by Nrg4. We investigated how Nrg4 regulates hepatic lipid metabolism in the fasting state and explored the effects of Nrg4 on adipose tissue gene expression, particularly those encoding secreted factors.
resultsAdipose Nrg4 expression is inversely correlated with adiposity and regulated by pro-inflammatory and anti-inflammatory signaling. Transgenic expression of Nrg4 increases energy expenditure and augments whole body glucose metabolism. Nrg4 protects mice from diet-induced hepatic steatosis in part through activation of hepatic fatty acid oxidation and ketogenesis. Finally, Nrg4 promotes a healthy adipokine profile during obesity.
conclusionsNrg4 exerts pleiotropic beneficial effects on energy balance and glucose and lipid metabolism to ameliorate obesity-associated metabolic disorders. Biologic therapeutics based on Nrg4 may improve both type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) in patients.
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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.