Overexpression of gankyrin induces liver steatosis in zebrafish (Danio rerio)
Journal
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Journal Volume
1811
Journal Issue
9
Pages
536-548
Date Issued
2011
Author(s)
DOI
BBMLF
Abstract
Gankyrin is a small ankyrin-repeat protein that previous research has confirmed to be overexpressed in hepatocellular carcinoma (HCC). Although relevant literature has reported on gankyrin functions in cellular proliferation and tumorigenesis, the exact role of gankyrin is poorly understood in animal model systems. This study analyzed hepatic lipid accumulation in gankyrin transgenic (GK) zebrafish. Bromodeoxyuridine (BrdU)-positive cells were predominantly increased in the liver bud of GK larvae, indicating that gankyrin functionally promoted cell proliferation at the larval stage in GK fish. However, over 90% of the viable GK adults showed an increased lipid content, leading in turn to liver steatosis. Liver histology and oil red O staining also indicated the accumulation of fatty droplets in GK fish, consistent with the specific pathological features of severe steatosis. Molecular analysis revealed that gankyrin overexpression induced hepatic steatosis and modulated the expression profiles of four hepatic microRNAs, miR-16, miR-27b, miR-122, and miR-126, and 22 genes involved in lipid metabolism. Moreover, significantly increased hepatic cell apoptosis resulted in liver damage in GK adults, leading to liver failure and death after approximately 10 months. This study is the first to report gankyrin as a potential link between microRNAs and liver steatosis in zebrafish. © 2011 Elsevier B.V. All Right Reserved.
Subjects
ACAT 2 protein; acetyl coenzyme A carboxylase; acyl coenzyme A desaturase; ankyrin; apolipoprotein A4; carnitine palmitoyltransferase I; CCAAT enhancer binding protein alpha; CD36 antigen; diacylglycerol acyltransferase 2; fat droplet; fatty acid binding protein; fatty acid binding protein 6; fatty acid synthase; gankyrin; low density lipoprotein receptor; LPIN1 protein; microRNA; microRNA 122; microRNA 126; microRNA 16; microRNA 27b; peroxisome proliferator activated receptor alpha; peroxisome proliferator activated receptor gamma; phosphatidate phosphatase; protein; slc25a10 protein; slc35b4 protein; slc6a19 protein; sterol regulatory element binding protein 1c; unclassified drug; uncoupling protein 2; animal cell; animal experiment; animal model; animal tissue; apoptosis; article; cell proliferation; cholestasis; controlled study; death; disease severity; embryo; fatty liver; female; gene expression profiling; gene overexpression; genetic analysis; larva; lipid liver level; lipid metabolism; lipid storage; lipid transport; liver cell; liver failure; liver histology; liver hyperplasia; liver injury; male; nonhuman; nucleotide sequence; priority journal; protein expression; signal transduction; staining; transgenic animal; zebra fish; Animals; Animals, Genetically Modified; Base Sequence; Fatty Liver; Female; Humans; Lipid Metabolism; Liver; Male; MicroRNAs; Molecular Sequence Data; Proteasome Endopeptidase Complex; Proto-Oncogene Proteins; Zebrafish; Zebrafish Proteins; Animalia; Danio rerio
SDGs
Type
journal article