Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.11 (AMPK)
 12,425 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous findings supported that fetuin B, a new hepatokine, may be involved in the development of hepatic steatosis, but the mechanism is still unknown. This study aims to investigate the role of fetuin B in hepatic steatosis in C57BL/6 mice and HepG2 cells. 1) We found that the administration of recombinant fetuin B aggravated hepatic lipid accumulation caused by free fatty acids (FFAs) or high fat diet, in vivo and in vitro. It lowered the phosphorylated AMPK levels and activated the LXR-SREBP1c pathway, accompanied by the downregulation of fatty acid oxidation and upregulation of lipogenesis. Furthermore, in HepG2 cells exposed to recombinant fetuin B and FFAs, the AMPK agonist depressed the LXR-SREBP1c pathway and alleviated lipid accumulation. The knockdown of LXR protected against steatosis but failed to change phosphorylated AMPK. 2) The knockdown of fetuin B by siRNA or shRNA alleviated lipid accumulation, in vivo and in vitro. It enhanced phosphorylated AMPK and depressed the LXR-SREBP1c pathway, accompanied by upregulation of fatty acid oxidation and downregulation of lipogenesis. Moreover, in HepG2 cells exposed to fetuin B siRNA and FFAs, LXR agonist aggravated lipid accumulation but failed to influence AMPK. This study indicated that fetuin B aggravated LXR-mediated hepatic steatosis through AMPK. It might offer new insights into clinical management and biomarker research on fatty liver.
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PMID:Fetuin B aggravates liver X receptor-mediated hepatic steatosis through AMPK in HepG2 cells and mice. 3097 77

Background: Liver transplantation leads to non-alcoholic fatty liver disease or non-alcoholic steatohepatitis in up to 40% of graft recipients. The aim of our study was to assess transcriptomic profiles of liver grafts and to contrast the hepatic gene expression between the patients after transplantation with vs. without graft steatosis. Methods: Total RNA was isolated from liver graft biopsies of 91 recipients. Clinical characteristics were compared between steatotic (n = 48) and control (n = 43) samples. Their transcriptomic profiles were assessed using Affymetrix HuGene 2.1 ST Array Strips processed in Affymetrix GeneAtlas. Data were analyzed using Partek Genomics Suite 6.6 and Ingenuity Pathway Analysis. Results: The individuals with hepatic steatosis showed higher indices of obesity including weight, waist circumference or BMI but the two groups were comparable in measures of insulin sensitivity and cholesterol concentrations. We have identified 747 transcripts (326 upregulated and 421 downregulated in steatotic samples compared to controls) significantly differentially expressed between grafts with vs. those without steatosis. Among the most downregulated genes in steatotic samples were P4HA1, IGF1, or fetuin B while the most upregulated were PLIN1 and ME1. Most influential upstream regulators included HNF1A, RXRA, and FXR. The metabolic pathways dysregulated in steatotic liver grafts comprised blood coagulation, bile acid synthesis and transport, cell redox homeostasis, lipid and cholesterol metabolism, epithelial adherence junction signaling, amino acid metabolism, AMPK and glucagon signaling, transmethylation reactions, and inflammation-related pathways. The derived mechanistic network underlying major transcriptome differences between steatotic samples and controls featured PPARA and SERPINE1 as main nodes. Conclusions: While there is a certain overlap between the results of the current study and published transcriptomic profiles of non-transplanted livers with steatosis, we have identified discrete characteristics of the non-alcoholic fatty liver disease in liver grafts potentially utilizable for the establishment of predictive signature.
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PMID:Hepatic Gene Expression Profiles Differentiate Steatotic and Non-steatotic Grafts in Liver Transplant Recipients. 3111 47