ArticleJCI insight2018
NRG1-Fc improves metabolic health via dual hepatic and central action.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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.
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Who cites it
30 citing papers in PubMed, 53 citations in OpenAlex.
- Single-cell transcriptomics reveals the impact of sex and age in the healthy human liver.JHEP reports : innovation in hepatology · 2026Article
- Neuregulin 4 in Insulin Resistance: Mechanisms, Controversies, and Therapeutic Perspectives.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- Ivermectin Binds to the Allosteric Site (Site 2) and Inhibits Allosteric Integrin Activation by TNF and Other Pro-Inflammatory Cytokines.International journal of molecular sciences · 2025Article
- Secreted proteins in treating metabolic dysfunction-associated steatotic liver disease: from bench towards bedside.Protein & cell · 2025Review
- Article
- Novel secreted regulators of glucose and lipid metabolism in the development of metabolic diseases.Diabetologia · 2024Review
- Discovery of NRG1-VII: the myeloid-derived class of NRG1.BMC genomics · 2024Article
- Neuregulin 4 mediates the metabolic benefits of mild cold exposure by promoting beige fat thermogenesis.JCI insight · 2024Article
- Energy Expenditure Homeostasis Requires ErbB4, an Obesity Risk Gene, in the Paraventricular Nucleus.eNeuro · 2023Article
- Neuregulin4 Acts on Hypothalamic ErBb4 to Excite Oxytocin Neurons and Preserve Metabolic Homeostasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Irisin ameliorates age-associated sarcopenia and metabolic dysfunction.Journal of cachexia, sarcopenia and muscle · 2023Article
- New players of the adipose secretome: Therapeutic opportunities and challenges.Current opinion in pharmacology · 2022Review
- Deconstructing a Syndrome: Genomic Insights Into PCOS Causal Mechanisms and Classification.Endocrine reviews · 2022Article
- Neuregulin 4 suppresses NASH-HCC development by restraining tumor-prone liver microenvironment.Cell metabolism · 2022Article
- Factors Associated with White Fat Browning: New Regulators of Lipid Metabolism.International journal of molecular sciences · 2022Review
- Relationship Between Hepatic Gene Expression, Intestinal Microbiota, and Inferred Functional Metagenomic Analysis in NAFLD.Clinical and translational gastroenterology · 2022Article
- The Role of Neuregulin-1 in Steatotic and Non-Steatotic Liver Transplantation from Brain-Dead Donors.Biomedicines · 2022Article
- Neuregulin-1, a potential therapeutic target for cardiac repair.Frontiers in pharmacology · 2022Review
- Serum neuregulin 4 is negatively correlated with insulin sensitivity in humans and impairs mitochondrial respiration in HepG2 cells.Frontiers in physiology · 2022Article
- GC-MS Profile of Hua-Feng-Dan and RNA-Seq Analysis of Induced Adaptive Responses in the Liver.Frontiers in pharmacology · 2022Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Neuregulins (NRGs) are emerging as an important family of signaling ligands that regulate glucose and lipid homeostasis. NRG1 lowers blood glucose levels in obese mice, whereas the brown fat-enriched secreted factor NRG4 protects mice from high-fat diet-induced insulin resistance and hepatic steatosis. However, the therapeutic potential of NRGs remains elusive, given the poor plasma half-life of the native ligands. Here, we engineered a fusion protein using human NRG1 and the Fc domain of human IgG1 (NRG1-Fc) that exhibited extended half-life in circulation and improved potency in receptor signaling. We evaluated its efficacy in improving metabolic parameters and dissected the mechanisms of action. NRG1-Fc treatment triggered potent AKT activation in the liver, lowered blood glucose, improved insulin sensitivity, and suppressed food intake in obese mice. NRG1-Fc acted as a potent secretagogue for the metabolic hormone FGF21; however, the latter was largely dispensable for its metabolic effects. NRG1-Fc directly targeted the hypothalamic POMC neurons to promote membrane depolarization and increase firing rate. Together, NRG1-Fc exhibits improved pharmacokinetic properties and exerts metabolic benefits through dual inhibition of hepatic gluconeogenesis and caloric intake.
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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.