Distinct modulatory roles for thyroid hormone receptors TRα and TRβ in SREBP1-activated ABCD2 expression

Weinhofer, Isabelle; Kunze, Markus; Rampler, Heidelinde; Forss‐Petter, Sonja; Samarut, Jacques; Plateroti, Michelina; Berger, Johannes

doi:10.1016/j.ejcb.2008.08.002

Cited by 25 publications

(14 citation statements)

References 35 publications

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“…ABCD2 is speculated to act as a dimerization partner of ABCD1, the X-linked adrenoleukodystrophy-associated protein (9), and has a functional redundancy with ABCD1. Therefore, mRNA expression levels of RXRα and THRβ, as well as PPARα and SREBP, which were reported to be regulators of ABCD2 expression were assessed (10). Only PPARα mRNA expression was found to be higher in the HFD mice than in the RD mice (Fig.…”

Section: Discussionmentioning

confidence: 99%

Induction of peroxisomal lipid metabolism in mice fed a high-fat diet

et al. 2011

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Abstract. Peroxisomes catalyze a range of essential metabolic functions, mainly related to lipid metabolism. However, their roles in obesity have yet to be clarified. The aim of this study was to investigate the correlation between obesity and peroxisomal lipid metabolism, particularly very long-chain fatty acid (VLCFA) metabolism, gene expression of peroxisomal β-oxidation enzymes, peroxisomal ATP-binding cassette (ABC) transporter adrenoleukodystrophy (ABCD1) gene and its related gene, ABCD2, the elongation of the VLCFA (ELOVL) gene family and the transcriptional factors involved in the regulation of these genes, including peroxisome proliferator-activated receptor α (PPARα) and sterol regulatory element-binding protein. These factors were analyzed in livers from mice fed a high-fat diet (HFD) or a regular diet (RD) for 20 weeks. Furthermore, the amounts of plasma saturated and unsaturated fatty acids, including VLCFAs, were measured. A HFD induced hepatic gene expression of not only hydroxysteroid 17-β dehydrogenase 4 (HSD17b4) and sterol carrier protein 2 (SCP2) in peroxisomal β-oxidation enzymes but also of ELOVL1, 2, 5 and 6, which are involved in the elongation of saturated and unsaturated VLCFAs. Furthermore, ABCD2 mRNA prominently increased in the HFD mice. The transcriptional regulator of these genes, PPARα, was also up-regulated in the HFD mice. VLCFA ratios including C24:0/ C22:0, C25:0/C22:0 and C26:0/C22:0 are the most significant diagnostic markers of inherited peroxisomal diseases. These ratios were found to be low in the plasma of the HFD mice compared with the RD mice. The results suggest that HFD activates hepatic peroxisomal VLCFA metabolism, and may provide useful fundamental information to explain the role of peroxisomal function in obesity and lifestyle-related diseases.

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Section: Discussionmentioning

confidence: 99%

Induction of peroxisomal lipid metabolism in mice fed a high-fat diet

et al. 2011

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“…Our previous study on the T3-response of the ABCD2 gene [18] and the recent work of Weinhofer et al [35] suggest that the ligand binding on TR␤1 results in a derepression of the Abcd2 promoter. In the current study, we addressed whether GC-1 and CGS 23425, two thyroid hormone homologs showing selectivity for the TR␤1 isoform, could induce the expression of the ABCD2 gene.…”

Section: Discussionmentioning

confidence: 96%

“…This is probably linked to the presence of TR␣1 in these cells [36] and to the capability of ABCD2 to be induced by T3 through TR␣1 activation [35]. The induction level observed after a treatment of 2 days was amplified with time reaching a maximum after 10 days.…”

Section: Discussionmentioning

confidence: 97%

Induction of the adrenoleukodystrophy-related gene (ABCD2) by thyromimetics

Génin

Gondcaille

Trompier

et al. 2009

The Journal of Steroid Biochemistry and Molecular Biology

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“…For these cases, pharmacological induction of the redundant gene ABCD2 , in the monocyte/macrophage lineage could be an alternative or additional treatment option. Extensive promoter analyses and former experiments suggested retinoids as promising candidate drugs for X-ALD [15], [21], [30]. Here, we tested the ability of retinoids to induce ABCD2 expression in human primary monocytes.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Retinoids for Induction of the Redundant Gene ABCD2 as an Alternative Treatment Option in X-Linked Adrenoleukodystrophy

et al. 2014

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X-linked adrenoleukodystrophy (X-ALD), the most common peroxisomal disorder, is a clinically heterogeneous disease that can manifest as devastating inflammatory cerebral demyelination (CALD) leading to death of affected males. Currently, the only curative treatment is allogeneic hematopoietic stem cell transplantation (HSCT). However, HSCT is only effective when performed at an early stage because the inflammation may progress for eighteen months after HSCT. Thus, alternative treatment options able to immediately halt the progression are urgently needed. X-ALD is caused by mutations in the ABCD1 gene, encoding the peroxisomal membrane protein ABCD1, resulting in impaired very long-chain fatty acid metabolism. The related ABCD2 protein is able to functionally compensate for ABCD1-deficiency both in vitro and in vivo. Recently, we demonstrated that of the cell types derived from CD34+ stem cells, predominantly monocytes but not lymphocytes are metabolically impaired in X-ALD. As ABCD2 is virtually not expressed in these cells, we hypothesize that a pharmacological up-regulation of ABCD2 should compensate metabolically and halt the inflammation in CALD. Retinoids are anti-inflammatory compounds known to act on ABCD2. Here, we investigated the capacity of selected retinoids for ABCD2 induction in human monocytes/macrophages. In THP-1 cells, 13-cis-retinoic acid reached the highest, fivefold, increase in ABCD2 expression. To test the efficacy of retinoids in vivo, we analyzed ABCD2 mRNA levels in blood cells isolated from acne patients receiving 13-cis-retinoic acid therapy. In treated acne patients, ABCD2 mRNA levels were comparable to pre-treatment levels in monocytes and lymphocytes. Nevertheless, when primary monocytes were in vitro differentiated into macrophages and treated with 13-cis-retinoic acid, we observed a fourfold induction of ABCD2. However, the level of ABCD2 induction obtained by retinoids alone is probably not of therapeutic relevance for X-ALD. In conclusion, our results suggest a change in promoter accessibility during macrophage differentiation allowing induction of ABCD2 by retinoids.

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Distinct modulatory roles for thyroid hormone receptors TRα and TRβ in SREBP1-activated ABCD2 expression

Cited by 25 publications

References 35 publications

Induction of peroxisomal lipid metabolism in mice fed a high-fat diet

Induction of peroxisomal lipid metabolism in mice fed a high-fat diet

Induction of the adrenoleukodystrophy-related gene (ABCD2) by thyromimetics

Evaluation of Retinoids for Induction of the Redundant Gene ABCD2 as an Alternative Treatment Option in X-Linked Adrenoleukodystrophy

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