ArticleCell death discovery2025
Impaired RelA signaling and lipid metabolism dysregulation in hepatocytes: driving forces in the progression of metabolic dysfunction-associated steatotic liver disease.
Article in Cell death discovery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 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
13 citing papers in PubMed.
- Review
- Integrated transcriptomic analysis identifies liver aging-driven fibrosis signatures and reveals therapeutic strategies based on medicine-food homology.NPJ science of food · 2026Article
- Miao Sour Soup Modulates Hepatic Gluconeogenesis Through PI3K/Akt/Foxo1 Signaling in High-Fat Diet-Induced Rats.Food science & nutrition · 2026Article
- Role of Sirtuin 6 in the Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease.Current issues in molecular biology · 2026Review
- Rebamipide Reprograms Hepatic Networks to Prevent and Reverse Metabolic-Dysfunction-Associated Steatotic Liver Disease: Multi-Omics Insights and Histological Validation.Pharmaceuticals (Basel, Switzerland) · 2026Article
- GATA2 deficiency exacerbates chronic liver injuryWorld journal of stem cells · 2026Article
- Preparation of sea cucumber collagen hydrolysate and its inhibitory effect on α-glucosidases.Food chemistry: X · 2026Article
- MAGL-18c attenuates LPS-induced sepsis-associated liver injury by inhibiting TGF-β/Smad signaling and remodeling medium- and long-chain fatty acid metabolism.Frontiers in immunology · 2026Article
- The role of bile acid-activated receptor TGR5 in inflammation and liver diseases.Frontiers in physiology · 2026Review
- Article
- Hepatocyte nuclear factors dynamically regulate triglyceride metabolic reprogramming in metabolic dysfunction-associated steatotic liver disease: Mechanisms and implications.World journal of hepatology · 2025Review
- Specnuezhenide mitigates tunicamycin-induced liver injury in mice via ER stress modulation and metabolic reprogramming.Molecular biology reports · 2025Article
- Identification of palmitoylated biomarkers in non-alcoholic fatty liver disease via integrated bioinformatics analysis and machine learning.Scientific reports · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RelA, also known as nuclear factor kappa B p65, plays a crucial role in the pathogenesis of various liver diseases. However, the specific role of RelA in hepatocytes during the progression of metabolic dysfunction-associated steatotic liver disease (MASLD) is not well understood. This study explored the relationship between impaired RelA signaling and lipid metabolism disorders in hepatocytes, and how they synergistically contribute to the advancement of MASLD. We assessed the changes, regulatory relationships, and impacts of RelA signaling and lipid metabolism remodeling on disease progression both in vitro and in vivo. During MASLD, there was a decrease in the expression of RelA and hepatocyte nuclear factor 1 alpha (HNF1α), with both factors showing mutual enhancement of each other's expression under normal conditions. This synergistic effect was absent during hepatocyte steatosis. RelA or HNF1α depletion in hepatocytes intensified MASLD symptoms, whereas overexpression of RELA or treatment with necrostatin-1 (a necroptosis inhibitor) or Z-VAD (a caspase inhibitor) significantly mitigated these effects. Mechanistically, during hepatic steatosis, altered lipid profiles exhibited lipotoxicity, inducing hepatocyte apoptosis and necroptosis, whereas endoplasmic reticulum (ER) stress triggered lipid remodeling processes similar to those observed in MASLD. RelA signaling upregulated the expression of activating transcription factor 4 and glucose-regulated protein 78, thereby alleviating ER stress. Impaired RelA signaling remodeled the ER stress response and lipid metabolism, and enhanced lipid accumulation and lipid toxicity. In conclusion, impaired RelA signaling and disrupted lipid metabolism form a detrimental feedback loop in hepatocytes that promotes MASLD progression. Lipid accumulation suppresses RelA signaling, remodeling the ER stress response and exacerbating lipid metabolism disorder, ultimately leading to hepatocyte apoptosis and necroptosis.
Identifiers
What Socratic 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 Socratic graph.