The Human Peroxisome Proliferator-activated Receptor δ Gene is a Primary Target of 1α,25-Dihydroxyvitamin D3 and its Nuclear Receptor

Dunlop, Thomas W.; Vaïsänen, Sami; Frank, Christian; Molnár, Ferdinand; Sinkkonen, Lasse; Carlberg, Carsten

doi:10.1016/j.jmb.2005.03.060

Cited by 195 publications

(139 citation statements)

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“…PPARs are considered as the sensors of the macronutrients fatty acids and their metabolites, whereas VDR acts as sensor for the metabolites of the micronutrient vitamin D. Both nuclear receptors control critical metabolic reactions as well as cellular growth (50). Moreover, we found that the PPAR␤/␦ gene is a primary VDR target (51), which suggests that both signaling systems may be even more tightly bound physiologically together. This places the PPAR-and VDR-responsive members of the IGFBP gene family into the position of critical interfaces in the response to these nuclear receptors, and hence through their ligands, dietary components and emphasizes their role as biomarkers in the metabolic syndrome as well as in cancer.…”

Section: Discussionmentioning

confidence: 83%

The Insulin-like Growth Factor-binding Protein 1 Gene Is a Primary Target of Peroxisome Proliferator-activated Receptors

Degenhardt

Matilainen

Herzig

et al. 2006

Journal of Biological Chemistry

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Insulin-like growth factor-binding protein 1 (IGFBP-1) is a biomarker for metabolic and hyperproliferative diseases. At the same time, the nuclear receptors peroxisome proliferator-activated receptors (PPARs) are known for their critical role in the development of both the metabolic syndrome and various cancers. Here we demonstrate, in human hepatocellular carcinoma cells and in normal mouse liver, that IGFBP-1 mRNA expression is under the primary control of PPAR ligands. We applied an improved in silico screening approach for PPAR response elements (PPREs) and identified five candidate PPREs located within 10 kb of the transcription start site (TSS) of the IGFBP-1 gene. Chromatin immunoprecipitation assays showed that, in living cells, the genomic region containing the most proximal PPRE, at position ؊1200 (relative to the TSS), preferentially associates with multiple PPAR subtypes and various other components of the transcriptional apparatus, which include their heterodimerizing partner, retinoid X receptor, as well as phosphorylated RNA polymerase II, co-repressor, co-activator, and mediator proteins. Moreover, further chromatin immunoprecipitation assays demonstrated that the TSS regions of the IGFBP-1 gene and those of the related IGFBP-2, -5, and -6, but not of IGFBP-3 and -4 genes, bind PPARs as well. We also show that these additional PPAR binding genes contain a number of candidate PPREs and that their mRNA levels respond quickly to the presence of PPAR ligands, indicating that they are also primary PPAR target genes.Lipid level dysregulation is a characteristic common to some of the most prevalent medical disorders, including obesity, cardiovascular disease, and type 2 diabetes (1). Nuclear receptor transcription factors may have important roles to play in these diseases, because many of them have lipophilic compounds as ligands, including fatty acids and their metabolic derivatives (2), which appear to be important in either the normal functioning or a role in the disease process affecting the metabolic pathways. For example, native and oxidized polyunsaturated fatty acids as well as arachidonic acid derivatives, such as prostaglandins and prostacyclins, selectively bind the nuclear receptors peroxisome proliferator-activated receptors (PPARs) 3 ␣, ␥, and ␤/␦ and stimulate their transcriptional activity (3). PPARs are prominent players in the metabolic syndrome, because they are important regulators of lipid storage and catabolism (4). However, PPARs also regulate cellular growth and differentiation and therefore have as well an impact on hyperproliferative diseases, such as cancer (5). PPAR␥ is the best characterized member of the subfamily due to its prominent role in the regulation of differentiation of cell types with active lipid metabolism, such as adipocytes and macrophage foam cells (6, 7). The importance of this receptor in lipid homeostasis and energy balance is accentuated by the widespread use of synthetic PPAR␥ ligands, such as the thiazolidinediones rosiglitazone, troglitazone, and piogl...

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Section: Discussionmentioning

confidence: 83%

The Insulin-like Growth Factor-binding Protein 1 Gene Is a Primary Target of Peroxisome Proliferator-activated Receptors

Degenhardt

Matilainen

Herzig

et al. 2006

Journal of Biological Chemistry

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“…44 The promotor region of certain human PPAR genes contains a potent VDRE (vitamin D response element). 46 In our regression models, we found significant associations with homozygous genotypes in 3 intronic SNPs in the PPARG gene with baseline 25-(OH) D levels, and another intronic SNP in the PPARG gene was marginally significant (p D 0.058). Although these were all intronic SNPs, it is possible they are in LD (linkage disequilibrium) with a functional SNP.…”

Section: Discussionmentioning

confidence: 59%

Vitamin D, leptin and impact on immune response to seasonal influenza A/H1N1 vaccine in older persons

Sadarangani

Ovsyannikova

Goergen

et al. 2015

Human Vaccines & Immunotherapeutics

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“…De multiples arguments expérimentaux sont en faveur d'un rôle protecteur direct ou indirect de la vitamine D contre le diabète de type 2 (Cormier et al, 2010) : -expression de la 1α-hydroxylase (Bland et al, 2004) et du VDR (Maestro et al, 2003) dans les cellules β du pancréas humain et expression d'éléments de réponse à la vitamine D dans le promoteur du gène humain de l'insuline (Johnson et al, 1994), -activation par le calcitriol de la transcription du gène humain de l'insuline (Maestro et al, 2002), -mise en évidence chez les souris invalidées pour le VDR d'une altération de la tolérance au glucose, d'une diminution de la capacité maximale de sécrétion d'insuline, cela indépendamment des modifications de calcémie (Zeitz et al, 2003), -stimulation par le calcitriol de l'expression du récepteur à l'insuline et du transport de glucose en réponse à l'insuline in vitro (Maestro et al, 2000), -activation directe par le calcitriol de PPARδ (peroxisome proliferator activator receptor δ = facteur de transcription impliqué dans la régulation du métabolisme glucidique dans le muscle et le tissu adipeux) (Dunlop et al, 2005), -concentration suffisante de 25(OH)D nécessaire au maintien de l'homéostasie calcique essentielle pour les processus intra cellulaires de réponse à l'insuline dans le muscle squelettique et le tissu adipeux (Draznin et al, 1987).…”

Section: Vitamine D Et Hormone Parathyroïdienne (Pth)unclassified

Vitamine D et santé cardiovasculaire

Courbebaisse

Cormier

2014

OCL

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Résumé -Le déficit en vitamine D touche environ 50 % de la population mondiale. Au-delà de ces effets classiques sur le métabolisme minéral, la vitamine D possède de nombreux effets extra osseux parmi lesquels des effets sur le système cardiovasculaire qui sont essentiellement documentés par des études observationnelles, expérimentales et par de petites études d'intervention s'intéressant la plupart du temps à des paramètres intermédiaires du risque cardiovasculaire. Il est de ce fait temps de conduire de larges études interventionnelles randomisées contre placebo, ciblant les effets de la vitamine D native sur les événements et la mortalité cardiovasculaire. Mots clés : Vitamine D / événements cardiovasculaires / diabèteAbstract -Vitamin D and cardiovascular health. Vitamin D deficiency affects almost 50% of the population worldwide. Besides its classical effects on bone and calcium metabolism, vitamin D displays a wide spectrum of non classical effects. Among these effects, those targeting the cardiovascular system are mostly documented by observational, experimental and small intervention trials that most often evaluated intermediate parameters. The time has now come for large placebo-controlled trials targeting clinical endpoints such as the incidence of major cardiovascular events and mortality.

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The Human Peroxisome Proliferator-activated Receptor δ Gene is a Primary Target of 1α,25-Dihydroxyvitamin D3 and its Nuclear Receptor

Cited by 195 publications

References 45 publications

The Insulin-like Growth Factor-binding Protein 1 Gene Is a Primary Target of Peroxisome Proliferator-activated Receptors

The Insulin-like Growth Factor-binding Protein 1 Gene Is a Primary Target of Peroxisome Proliferator-activated Receptors

Vitamin D, leptin and impact on immune response to seasonal influenza A/H1N1 vaccine in older persons

Vitamine D et santé cardiovasculaire

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