ArticlePloS one2021
Is there a role for neuregulin 4 in human nonalcoholic fatty liver disease?
Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 2 of them syntheses that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
6 citing papers in PubMed, 2 syntheses or guidelines pooled it, 13 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
- Neuregulin 4 in Insulin Resistance: Mechanisms, Controversies, and Therapeutic Perspectives.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- Novel secreted regulators of glucose and lipid metabolism in the development of metabolic diseases.Diabetologia · 2024Review
- Neuregulin-4 attenuates diabetic cardiomyopathy by regulating autophagy via the AMPK/mTOR signalling pathway.Cardiovascular diabetology · 2022Article
- Neuregulin 4 as a novel adipokine in energy metabolism.Frontiers in physiology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNeuregulin 4 (Nrg4), a novel adipokine enriched in brown adipose tissue has been observed to negatively regulate de novo hepatic lipogenesis and limit nonalcoholic fatty liver disease (NAFLD) progression to nonalcoholic steatohepatitis (NASH) in rodents. However, the role of Nrg4 in human NAFLD remains unclear to date. We analysed Nrg4 plasma levels and its association with liver disease severity together with the transcriptional profile of the Nrg4 pathway in liver and visceral adipose tissue (VAT) of NAFLD patients.
methodsPlasma Nrg4 levels were measured in 65 NAFLD patients and 43 healthy controls (HC). Hepatic steatosis and fibrosis were diagnosed and quantified with chemical shift MRI and transient elastography respectively. Furthermore, blood lipid levels, HOMA-IR and systemic pro-inflammatory cytokines (TNF-α, IL-6 and IFN-γ) were analysed. Microarray analyses to assess differences in the Nrg4 and its receptor family ErbB pathway in liver and VAT from an independent patient group with biopsy proven NAFL (simple steatosis) (n = 4), NASH (n = 5) and normal liver (n = 6) were performed.
resultsPlasma Nrg4 levels were not significantly different between NAFLD patients and HC (p = 0.622). Furthermore, plasma Nrg4 levels did not correlate with the hepatic fat fraction (r = -0.028, p = 0.829) and were not significantly different between NAFLD patients with or without hepatic fibrosis (p = 0.087). Finally, the expression profile of 82 genes related to the Nrg4-ErbB pathway in liver and VAT was not significantly different between NAFL, NASH or obese controls.
conclusionOur study does not support a role for Nrg4 in the pathophysiology of human NAFLD.
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