Global effects of vitamin A deficiency on gene expression in rat liver: evidence for hypoandrogenism

McClintick, Jeanette N.; Crabb, David W.; Tian, Huijun; Pinaire, Jane; Smith, Jennifer; Jerome, Ronald E.; Edenberg, Howard J.

doi:10.1016/j.jnutbio.2005.08.006

Cited by 30 publications

(24 citation statements)

References 51 publications

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“…However, in diet-induced obese mice atRA treatment decreased hepatic triglyceride content (Berry and Noy, 2009) and hepatic lipid accumulation (Kim et al, 2014). In contrast, in rats vitamin A deficiency led to increased expression of genes involved in fatty acid metabolism in the liver (McClintick et al, 2006) and decreased liver total phospholipid content and phosphatidylcholine synthesis (Oliveros et al, 2007), demonstrating opposite effects to those observed in mice. Low retinol diet also significantly decreased stellate cell free fatty acids and total lipids, whereas high retinol diet increased triglycerides, cholesteryl esters, free fatty acids, and total lipids in rat stellate cells (Moriwaki et al, 1988).…”

Section: Introductionmentioning

confidence: 94%

RETRACTION: All-Trans-Retinoic Acid Enhances Mitochondrial Function in Models of Human Liver

Tripathy

Chapman

Han

et al. 2016

Molecular Pharmacology

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All-trans-retinoic acid (atRA) is the active metabolite of vitamin A. The liver is the main storage organ of vitamin A, but activation of the retinoic acid receptors (RARs) in mouse liver and in human liver cell lines has also been shown. Although atRA treatment improves mitochondrial function in skeletal muscle in rodents, its role in modulating mitochondrial function in the liver is controversial, and little data are available regarding the human liver. The aim of this study was to determine whether atRA regulates hepatic mitochondrial activity. atRA treatment increased the mRNA and protein expression of multiple components of mitochondrial b-oxidation, tricarboxylic acid (TCA) cycle, and respiratory chain. Additionally, atRA increased mitochondrial biogenesis in human hepatocytes and in HepG2 cells with and without lipid loading based on peroxisome proliferator activated receptor gamma coactivator 1a and 1b and nuclear respiratory factor 1 mRNA and mitochondrial DNA quantification. atRA also increased b-oxidation and ATP production in HepG2 cells and in human hepatocytes. Knockdown studies of RARa, RARb, and PPARd revealed that the enhancement of mitochondrial biogenesis and b-oxidation by atRA requires peroxisome proliferator activated receptor delta. In vivo in mice, atRA treatment increased mitochondrial biogenesis markers after an overnight fast. Inhibition of atRA metabolism by talarozole, a cytochrome P450 (CYP) 26 specific inhibitor, increased the effects of atRA on mitochondrial biogenesis markers in HepG2 cells and in vivo in mice. These studies show that atRA regulates mitochondrial function and lipid metabolism and that increasing atRA concentrations in human liver via CYP26 inhibition may increase mitochondrial biogenesis and fatty acid b-oxidation and provide therapeutic benefit in diseases associated with mitochondrial dysfunction.

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Section: Introductionmentioning

confidence: 94%

RETRACTION: All-Trans-Retinoic Acid Enhances Mitochondrial Function in Models of Human Liver

Tripathy

Chapman

Han

et al. 2016

Molecular Pharmacology

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“…In addition, treatment with ATRA increased the rate of oxidation of an exogenously administered fatty acid in human HepG2 hepatoma cells (Amengual J, Ribot J and Palou A, submitted manuscript). However, others have reported a shift towards increased fat catabolism in liver of rats with vitamin A deficiency [25,26]. Moreover, high doses of retinoids can induce hypertriglyceridemia in rats and humans, an effect that appears to involve both increased hepatic production of VLDL and suppression of lipoprotein lipase activity in peripheral tissues (see [55]).…”

Section: Discussionmentioning

confidence: 99%

“…However, studies regarding the effects of vitamin A or its derivates on liver lipid metabolism have lead to controversial results. For instance, vitamin A deficiency has been reported to associate with both reduced [24] and enhanced [25,26] hepatic fat catabolism.…”

Section: Introductionmentioning

confidence: 99%

Retinoic Acid Treatment Enhances Lipid Oxidation and Inhibits Lipid Biosynthesis Capacities in the Liver of Mice

Amengual

Ribot

Bonet

et al. 2010

Cell Physiol Biochem

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Vitamin A, mainly as retinoic acid (RA), is known to affect the development and function of adipose tissues. Treatment with RA reduces body weight and adiposity independent of changes in food intake in mice. Lipid metabolism in liver can have a major impact on whole body adiposity. The aim of this work was to investigate the effects of an in vivo treatment with RA on hepatic lipid metabolism in mice. Adult, standard diet-fed mice were treated with different doses of all-trans RA or vehicle (subcutaneous injection) for 4 days before sacrifice. Food intake and body weight changes during treatment were determined, as well as adiposity, liver composition, levels of circulating metabolites and lipoproteins and expression levels of key mRNA species in liver following sacrifice. RA treatment resulted in reduced body weight and adiposity, as expected. In the liver, RA treatment triggered an increase in the mRNA expression levels of peroxisome proliferator-activated receptor alpha, retinoid X receptor alpha, uncoupling protein 2, liver-type carnitine palmitoyltransferase 1, and carnitine/acylcarnitine carrier, and a reduction in the mRNA expression levels of sterol regulatory element binding protein 1c and fatty acid synthase. Consistent with the changes in gene expression, hepatic triacylglycerol content and circulating VLDL fraction were reduced and levels of circulating ketone bodies increased after RA treatment. These results point to a capacity of active vitamin A forms to shift liver lipid metabolism in vivo towards increased catabolism and reduced lipogenesis. These effects might contribute to the reduction of adiposity brought about by RA treatment.

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“…We fi rst became aware of the retinoid inducibility of rat CYP2C70, now CYP2C22, based on microarray studies of retinoid-inducible genes in the liver of rats. CYP2C22 was listed as a gene more highly expressed in vitamin A-suffi cient than vitamin A-defi cient liver ( 27 ) and induced in liver by targretin and 4-hydroxyphenylretinamide ( 28 ), analogs of RA with potential chemotherapeutic properties. However, biochemical studies to characterize the mode of regulation of CYP2C22 expression and function to determine its enzymatic activity have not been reported.…”

Section: Gene Cloning and Construction Of Plasmidsmentioning

confidence: 99%

Liver-specific cytochrome P450 CYP2C22 is a direct target of retinoic acid and a retinoic acid-metabolizing enzyme in rat liver

Qian

Zolfaghari

Ross

2010

Journal of Lipid Research

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Global effects of vitamin A deficiency on gene expression in rat liver: evidence for hypoandrogenism

Cited by 30 publications

References 51 publications

RETRACTION: All-Trans-Retinoic Acid Enhances Mitochondrial Function in Models of Human Liver

RETRACTION: All-Trans-Retinoic Acid Enhances Mitochondrial Function in Models of Human Liver

Retinoic Acid Treatment Enhances Lipid Oxidation and Inhibits Lipid Biosynthesis Capacities in the Liver of Mice

Liver-specific cytochrome P450 CYP2C22 is a direct target of retinoic acid and a retinoic acid-metabolizing enzyme in rat liver

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