ArticleThe Journal of clinical investigation2017
Hepatic neuregulin 4 signaling defines an endocrine checkpoint for steatosis-to-NASH progression.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers.
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Who cites it
100 citing papers in PubMed, 166 citations in OpenAlex.
- Targeting receptor tyrosine kinases: from molecular mechanisms to clinical therapeutics.Signal transduction and targeted therapy · 2026Review
- Systemic metabolic dysfunction drives platelet-mediated inflammation, fibrogenesis, and hepatocarcinogenesis in metabolic dysfunction-associated steatotic liver disease.Clinical and molecular hepatology · 2026Review
- Hepatic Sirt2-PARP1-HMGB1 axis promotes exercise-mediated amelioration of MASH in mice.Science China. Life sciences · 2026Article
- The E3 Ligase RNF8 Promotes Ubiquitination and Degradation of ChREBPα During Liver Stress Response.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- THEMIS attenuates MASH by suppressing disease-associated hepatocyte induction and hepatocyte senescence in mice.The Journal of clinical investigation · 2026Article
- c-FLIP as a master regulator of immune homeostasis and disease mechanisms.Cell death & disease · 2026Review
- Metabolic dysfunction-associated steatotic liver disease and steatohepatitis-associated hepatocarcinoma preclinical models.Nature reviews. Gastroenterology & hepatology · 2026Review
- Interleukin-39 aggravates sepsis by inducing self-sustaining neutrophil activation in the lungs via the CXCL1-CXCR2 pathway.International journal of biological sciences · 2026Article
- Liver-nervous system axis in MASLD: mechanistic insights and emerging targeted therapies.eGastroenterology · 2026Review
- Article
- Ferroptosis in the pathogenesis of diabetic cardiomyopathy: mechanisms and therapeutic potential.Cardiovascular diabetology · 2025Review
- Secreted proteins in treating metabolic dysfunction-associated steatotic liver disease: from bench towards bedside.Protein & cell · 2025Review
- Nrg4 Secreted by Brown Adipose Tissue Suppresses Ferroptosis of Sepsis-Induced Liver Injury.Inflammation · 2025Article
- Inflammation in MASLD progression and cancer.JHEP reports : innovation in hepatology · 2025Review
- CD47-mediated regulation of glucose and lipid metabolism: implications for the pathogenesis of MASLD.Frontiers in endocrinology · 2025Review
- Neuregulin 4 attenuates pancreatic β-cell apoptosis induced by lipotoxicity via activating mTOR-mediated autophagy.Islets · 2024Article
- Novel secreted regulators of glucose and lipid metabolism in the development of metabolic diseases.Diabetologia · 2024Review
- Signaling through the nicotinic acetylcholine receptor in the liver protects against the development of metabolic dysfunction-associated steatohepatitis.PLoS biology · 2024Article
- From NAFLD to NASH: Understanding the spectrum of non-alcoholic liver diseases and their consequences.Heliyon · 2024Review
- Article
40 more citing papers are in PubMed but not listed here.
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9 authors at 4 institutions in 3 countries.
Funding
Abstract
Nonalcoholic steatohepatitis (NASH) is characterized by progressive liver injury, inflammation, and fibrosis; however, the mechanisms that govern the transition from hepatic steatosis, which is relatively benign, to NASH remain poorly defined. Neuregulin 4 (Nrg4) is an adipose tissue-enriched endocrine factor that elicits beneficial metabolic effects in obesity. Here, we show that Nrg4 is a key component of an endocrine checkpoint that preserves hepatocyte health and counters diet-induced NASH in mice. Nrg4 deficiency accelerated liver injury, fibrosis, inflammation, and cell death in a mouse model of NASH. In contrast, transgenic expression of Nrg4 in adipose tissue alleviated diet-induced NASH. Nrg4 attenuated hepatocyte death in a cell-autonomous manner by blocking ubiquitination and proteasomal degradation of c-FLIPL, a negative regulator of cell death. Adeno-associated virus-mediated (AAV-mediated) rescue of hepatic c-FLIPL expression in Nrg4-deficent mice functionally restored the brake for steatosis to NASH transition. Thus, hepatic Nrg4 signaling serves as an endocrine checkpoint for steatosis-to-NASH progression by activating a cytoprotective pathway to counter stress-induced liver injury.
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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.