Age-Stratified Glycolysis and Bile Acid Metabolism Drive Survival in Acute Liver Failure: Insights from NCBI Pathways
Year: 2025
Type: article
Abstract: Objective: This study investigates age-dependent variations in hepatic glycolytic adaptation during Dgalactosamine-induced acute liver failure (ALF), identifying metabolic regulators through integrated bioinformatics analyses leveraging NCBI-annotated datasets.Methods: Age-stratified male Wistar rats (6-week juvenile vs 8-month middle-aged) received D-GalN (YDI/MDI) or PBS.Multi-omics analysis combining hepatic transcriptomics, serum enzyme analyses, and qPCR validation was conducted at 24h post-challenge.Multi-omics pathway analysis incorporated NCBI GEO/KEGG resources.Results: Juvenile rats exhibited 37.5% survival versus 100% mortality in middle-aged counterparts (p<0.001).Juvenile livers demonstrated 245-fold Gck induction with coordinated glycolytic activation (Pfkfb3/4↑, Fbp2↓), contrasting with metabolic paralysis in aged rats.Bile acid signaling mediated Pfkfb3/4 activation (r=0.82) and gluconeogenic suppression (Pck1↓).Acat2/2l1-driven cholesterol esterification attenuated lipotoxicity through FFA reduction.Human ALF validation revealed age-dependent Gck (Log2FC=-3.1) and Acat2 (Log2FC=-2.8)suppression (p<0.05).Conclusion: Juvenile hepatic resilience stems from bile acid-potentiated glycolysis and Acat2-mediated lipid detoxification -pathways impaired in aging.Our translational framework identifies Gck activation and Acat2 induction as age-stratified therapeutic strategies, highlighting INT-777 (TGR5 agonist) as a candidate for metabolic reprogramming in geriatric ALF.
Source: Research Review
Author: xiuwen Wang
Institution: Jilin Normal University
Language: English
Subfield: Pharmacology
Domain: Life Sciences
Open Access status: diamond
Awards: G3019833967, G4758755229, G5033337591
OpenAlex ID: W4410211888