Different regulation of the LXRα promoter activity by isoforms of CCAAT/enhancer-binding proteins

Steffensen, Knut R.; Schuster, Gertrud U.; Parini, P.; Holter, Elin; Sadek, Christine M.; Cassel, Tobias N.; Eskild, Winnie; Gustafsson, Jan‐Åke

doi:10.1016/s0006-291x(02)00390-x

Cited by 25 publications

(17 citation statements)

References 40 publications

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“…1B, AEBP1 is capable of repressing PPAR␥1 expression in a doseresponsive manner, despite transfection of equal DNA amounts by using empty vector. Consistently, cotransfection analysis using the pGL3-mouse LXR␣ (mLXR␣)-luciferase construct (21) reveals that LXR␣ expression is negatively regulated by AEBP1 in a dose-responsive manner (Fig. 1B).…”

supporting

confidence: 68%

Adipocyte enhancer-binding protein 1 is a potential novel atherogenic factor involved in macrophage cholesterol homeostasis and inflammation

Majdalawieh

Zhang

Fuki

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Peroxisome proliferator-activated receptor ␥1 (PPAR␥1) and liver X receptor ␣ (LXR␣) play pivotal roles in macrophage cholesterol homeostasis and inflammation, key biological processes in atherogenesis. Herein we identify adipocyte enhancer-binding protein 1 (AEBP1) as a transcriptional repressor that impedes macrophage cholesterol efflux, promoting foam cell formation, via PPAR␥1 and LXR␣ down-regulation. Contrary to AEBP1 deficiency, AEBP1 overexpression in macrophages is accompanied by decreased expression of PPAR␥1, LXR␣, and their target genes ATP-binding cassette A1, ATP-binding cassette G1, apolipoprotein E, and CD36, with concomitant elevation in IL-6, TNF-␣, monocyte chemoattractant protein 1, and inducible NO synthase levels. AEBP1, but not the C-terminally truncated DNA-binding domain mutant (AEBP1 ⌬Sty ), represses PPAR␥1 and LXR␣ in vitro. Expectedly, AEBP1-overexpressing transgenic (AEBP1 TG ) macrophages accumulate considerable amounts of lipids compared with AEBP1 nontransgenic macrophages, making them precursors for foam cells. Indeed, AEBP1-overexpressing transgenic macrophages exhibit diminished cholesterol efflux compared with AEBP1 nontransgenic macrophages, whereas AEBP1-knockout (AEBP1 ؊/؊ ) macrophages exhibit enhanced cholesterol efflux compared with wild-type (AEBP1 ؉/؉ ) macrophages. Our in vitro and ex vivo experimental data strongly suggest that AEBP1 plays critical regulatory roles in macrophage cholesterol homeostasis, foam cell formation, and proinflammation. Thereby, we speculate that AEBP1 may be critically implicated in the development of atherosclerosis, and it may serve as a molecular target toward developing antiinflammatory, antiatherogenic therapeutic approaches.atherogenesis ͉ cholesterol efflux ͉ liver X receptor ␣ ͉ peroxisome proliferator-activated receptor ␥

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supporting

confidence: 68%

Adipocyte enhancer-binding protein 1 is a potential novel atherogenic factor involved in macrophage cholesterol homeostasis and inflammation

Majdalawieh

Zhang

Fuki

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…Compared to DEX, exposure to the PBDE mixture, DE-71, or BDE-47 resulted in the late induction of PPARγ and C/EBPα on days 5-8, which in turn was sufficient to induce the adipogenic factor, LXRα [20]–[22]. It has been postulated that LXRα regulates lipogenesis and maintenance of the mature adipocyte phenotype, but not adipogenesis itself [23].…”

Section: Discussionmentioning

confidence: 99%

Induction of Adipocyte Differentiation by Polybrominated Diphenyl Ethers (PBDEs) in 3T3-L1 Cells

et al. 2014

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Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants that were extensively used in commercial products. PBDEs are ubiquitous environmental contaminants that are both lipophilic and bioaccumulative. Effects of PBDEs on adipogenesis were studied in the 3T3-L1 preadipocyte cell model in the presence and absence of a known adipogenic agent, dexamethasone (DEX). A PBDE mixture designed to mimic body burden of North Americans was tested, in addition to the technical mixture DE-71 and the individual congener BDE-47. The mixture, DE-71, and BDE-47 all induced adipocyte differentiation as assessed by markers for terminal differentiation [fatty acid binding protein 4 (aP2) and perilipin] and lipid accumulation. Characterization of the differentiation process in response to PBDEs indicated that adipogenesis induced by a minimally effective dose of DEX was enhanced by these PBDEs. Moreover, C/EBPα, PPARγ, and LXRα were induced late in the differentiation process. Taken together, these data indicate that adipocyte differentiation is induced by PBDEs; they act in the absence of glucocorticoid and enhance glucocorticoid-mediated adipogenesis.

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“…Although expression of LXRα is upregulated during fat cell differentiation, LXRβ is not regulated by adipogenesis. 11, 12, 13 Three different splice variants of LXRα 1, 2, 3 have been reported, where the most abundant and active form is the LXRα1 variant, which is present in all tissues expressing LXRα. 14 LXRα2 is predominantly expressed in human testis and cancer cell lines, and lacks the first 45 amino acids present in LXRα1.…”

Section: Lxr Genes and Expression In Adipose Tissuementioning

confidence: 99%

“…Different studies have reported stimulation, no effect or even suppression of adipogenesis by LXR ligands. In murine 3T3-L1 cells and human in vitro -differentiated Simpson-Golabi-Behmel syndrome (SGBS) pre-adipocyte cells, LXR expression is regulated by PPARγ and C/EBPα 11, 13, 40, 41 —two transcription factors indispensible for adipogenesis. Functional PPARγ-binding elements are present in both the murine and human LXRα gene.…”

Section: Role Of Lxr In Adipogenesismentioning

confidence: 99%

Liver X receptors and fat cell metabolism

Laurencikiene

Rydén

2012

Int J Obes

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Liver X receptors (LXRs) are members of the nuclear receptor family and are present in two isoforms, α and β, encoded by two separate genes. Originally described in the liver, LXRs have in the last 15 years been implicated in central metabolic pathways, including bile acid synthesis, lipid and glucose homeostasis. Although the vast majority of studies have been performed in non-adipose cells/tissues, results in recent years suggest that LXRs may have important modulatory roles in adipose tissue and adipocytes. Although several authors have published reviews on LXR, there have been no attempts to summarize the effects reported specifically in adipose systems. This overview gives a brief introduction to LXR and describes the sometimes-contradictory results obtained in murine cell systems and in rodent adipose tissue. The so far very limited number of studies performed in human adipocytes and adipose tissue are also presented. It should be apparent that although LXR may impact on several different pathways in metabolism, the clinical role of LXR modulation in adipose tissue is still not clear.

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Different regulation of the LXRα promoter activity by isoforms of CCAAT/enhancer-binding proteins

Cited by 25 publications

References 40 publications

Adipocyte enhancer-binding protein 1 is a potential novel atherogenic factor involved in macrophage cholesterol homeostasis and inflammation

Adipocyte enhancer-binding protein 1 is a potential novel atherogenic factor involved in macrophage cholesterol homeostasis and inflammation

Induction of Adipocyte Differentiation by Polybrominated Diphenyl Ethers (PBDEs) in 3T3-L1 Cells

Liver X receptors and fat cell metabolism

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