原创力文档the hepatic raldh1 expression is elevated in zucker fatty rats and its over-expression introduced the retinal-induced srebp-1c expression in ins-1 cellszucker肥鼠肝的小鼠表达水平升高及其表达介绍了retinal-induced srebp-1c ins-1细胞中表达.pdfVIP
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the hepatic raldh1 expression is elevated in zucker fatty rats and its over-expression introduced the retinal-induced srebp-1c expression in ins-1 cellszucker肥鼠肝的小鼠表达水平升高及其表达介绍了retinal-induced srebp-1c ins-1细胞中表达
The Hepatic Raldh1 Expression Is elevated in Zucker
Fatty Rats and Its Over-Expression Introduced the
Retinal-Induced Srebp-1c Expression in INS-1 Cells
Yang Li, Yan Zhang, Rui Li, Wei Chen, Meredith Howell, Rui Zhang, Guoxun Chen*
Department of Nutrition, the University of Tennessee at Knoxville, Knoxville, Tennessee, United States of America
Abstract
The roles of vitamin A (VA) in the development of metabolic diseases remain unanswered. We have reported that retinoids
synergized with insulin to induce the expression of sterol-regulatory element-binding protein 1c gene (Srebp-1c) expression
in primary rat hepatocytes. Additionally, the hepatic Srebp-1c expression is elevated in Zucker fatty (ZF) rats, and reduced in
those fed a VA deficient diet. VA is metabolized to retinoic acid (RA) for regulating gene expression. We hypothesized that
the expression of RA production enzymes contributes to the regulation of the hepatic Srebp-1c expression. Therefore, we
analyzed their expression levels in Zucker lean (ZL) and ZF rats. The mRNA levels of retinaldehyde dehydrogenase family 1
gene (Raldh1) were found to be higher in the isolated and cultured primary hepatocytes from ZF rats than that from ZL rats.
The RALDH1 protein level was elevated in the liver of ZF rats. Retinol and retinal dose- and time-dependently induced the
expression of RA responsive Cyp26a1 gene in hepatocytes and hepatoma cells. INS-1 cells were identified as an ideal tool to
study the effects of RA production on the regulation of gene expression because only RA, but not retinal, induced Srebp-1c
mRNA expression in them. Recombinant adenovirus containing rat Raldh1 cDNA was made and used to infect INS-1 cells.
The over-expression of RALDH1 introduced the retinal-mediated induction of Srebp-1c expression in INS-1 cells. We
conclude that the expression levels of the enzymes for R
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