ArticlePloS one2012
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.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 29 citations in OpenAlex.
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- Doxorubicin Attenuates Free Fatty Acid-Induced Lipid Accumulation via Stimulation of p53 in HepG2 Cells.Biomolecules & therapeutics · 2024Article
- All-trans retinoic acid impairs glucose-stimulated insulin secretion by activating the RXR/SREBP-1c/UCP2 pathway.Acta pharmacologica Sinica · 2022Article
- Replenishment of vitamin A for 7 days partially restored hepatic gene expressions altered by its deficiency in rats.Frontiers in nutrition · 2022Article
- Review
- Higher protein kinase C ζ in fatty rat liver and its effect on insulin actions in primary hepatocytes.PloS one · 2015Article
- Retinaldehyde dehydrogenase 1 deficiency inhibits PPARγ-mediated bone loss and marrow adiposity.Bone · 2014Article
- Aldehyde dehydrogenase 1A1: friend or foe to female metabolism?Nutrients · 2014Review
- The expression of Apoc3 mRNA is regulated by HNF4α and COUP-TFII, but not acute retinoid treatments, in primary rat hepatocytes and hepatoma cells.Molecular and cellular biochemistry · 2014Article
- Inflammation rapidly modulates the expression of ALDH1A1 (RALDH1) and vimentin in the liver and hepatic macrophages of rats in vivo.Nutrition & metabolism · 2014Article
- Vitamin A and feeding statuses modulate the insulin-regulated gene expression in Zucker lean and fatty primary rat hepatocytes.PloS one · 2014Article
- Roles of Vitamin A Metabolism in the Development of Hepatic Insulin Resistance.ISRN hepatology · 2013Review
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Authors and funding
7 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
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 RA production may contribute to the regulation of RA responsive genes, and determine the responses of the cells to retinoid treatments. The elevated hepatic expression of Raldh1 in ZF rats may cause the excessive RA production from retinol, and in turn, result in higher Srebp-1c expression. This excessive RA production may be one of the factors contributing to the elevated lipogenesis in the liver of ZF rats.
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