Molecular cloning and characterization of rat brain endothelial cell derived gene-1 (tumor suppressor candidate 5) expressing abundantly in adipose tissues

Shibata, Takahisa; Koide, Hisashi; Hayashi, Ryosuke; Nagata, Kiyoshi; Takeo, Chikari; Yoshida, Tomohiko; Noguchi, Yoshihiko; Tanaka, Tomoaki; Saitō, Yasushi; Tatsuno, Ichiro

doi:10.1016/j.mce.2006.08.007

Cited by 12 publications

(14 citation statements)

References 22 publications

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“…Only one other study has addressed this question, using Zucker fatty rats that lack proper leptin signaling and therefore become extremely obese: Tusc5 mRNA and protein levels were very slightly increased in subcutaneous WAT, unchanged in mesenteric, and yet decreased substantially in epididymal WAT [4]. We observed no significant difference between adult obese and non-obese women in terms of WAT Tusc5 transcript levels (Figure 5).…”

Section: Discussionmentioning

confidence: 74%

“…Findings to date indicate that cold ambient temperature markedly reduces rodent WAT and BAT Tusc5 mRNA levels, and Tusc5 expression rises during adipogenesis in white and brown adipocytes [2, 4, 5]. The cold-suppression of Tusc5 expression does not appear to be via activation of β 3-adrenergic receptors [5].…”

Section: Discussionmentioning

confidence: 99%

“…Consistent with this postulate, Tusc5 protein contains a CD225 interferon-induced transmembrane protein domain [2], found in the archetypal interferon-responsive 9–27 protein that is implicated in antiproliferative actions of interferons [3]. It is now firmly established that Tusc5 expression is remarkably tissue specific in rodents and humans, with robust expression in mature white and brown adipocytes [2, 4, 5] and in peripheral afferent neurons [2]. This unique expression pattern suggests an important function for Tusc5 in both adipose tissue and the peripheral nervous system.…”

Section: Introductionmentioning

confidence: 89%

“…This model was based largely on the putative tumor suppressor features of Tusc5 (see above), coincident expression of Tusc5 with adipocyte markers that increase as 3T3-L1 adipocytes exit the mitotic clonal expansion phase to terminally differentiate and mature [2], and the repression of Tusc5 expression in the “proliferative” brown adipose tissue (BAT) of cold exposed rodents ([4]; also see [2]). According to this model, Tusc5 has a “governor” role that would be dampened when adipocyte growth cues are triggered (i.e., by cold or obesity).…”

Section: Introductionmentioning

confidence: 99%

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Molecular Characterization of the Tumor Suppressor Candidate 5 Gene: Regulation by PPARγ and Identification of TUSC5 Coding Variants in Lean and Obese Humans

et al. 2009

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Tumor suppressor candidate 5 (TUSC5) is a gene expressed abundantly in white adipose tissue (WAT), brown adipose tissue (BAT), and peripheral afferent neurons. Strong adipocyte expression and increased expression following peroxisome proliferator activated receptor γ (PPARγ) agonist treatment of 3T3-L1 adipocytes suggested a role for Tusc5 in fat cell proliferation and/or metabolism. However, the regulation of Tusc5 in WAT and its potential association with obesity phenotypes remain unclear. We tested the hypothesis that the TUSC5 gene is a bona fide PPARγ target and evaluated whether its WAT expression or single-nucleotide polymorphisms (SNPs) in the TUSC5 coding region are associated with human obesity. Induction of Tusc5 mRNA levels in 3T3-L1 adipocytes by troglitazone and GW1929 followed a dose-response consistent with these agents' binding affinities for PPARγ. Chromatin immunoprecipitation (ChIP) experiments confirmed that PPARγ protein binds a ∼ −1.1 kb promotor sequence of murine TUSC5 transiently during 3T3-L1 adipogenesis, concurrent with histone H3 acetylation. No change in Tusc5 mRNA or protein levels was evident in type 2 diabetic patients treated with pioglitazone. Tusc5 expression was not induced appreciably in liver preparations overexpressing PPARs, suggesting that tissue-specific factors regulate PPARγ responsiveness of the TUSC5 gene. Finally, we observed no differences in Tusc5 WAT expression or prevalence of coding region SNPs in lean versus obese human subjects. These studies firmly establish the murine TUSC5 gene locus as a PPARγ target, but the significance of Tusc5 in obesity phenotypes or in the pharmacologic actions of PPARγ agonists in humans remains equivocal.

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Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

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Molecular Characterization of the Tumor Suppressor Candidate 5 Gene: Regulation by PPARγ and Identification of TUSC5 Coding Variants in Lean and Obese Humans

et al. 2009

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“…Through transcriptome analysis of temperature-dependent gene expression changes in thermogenic mouse brown adipose tissue (BAT),14 we previously characterized a cold-repressed white adipose tissue (WAT) and BAT gene (1) termed tumor suppressor candidate 5 (Tusc5). Rat Tusc5 has been identified as a BAT and WAT gene downregulated by cold exposure and induced during brown adipocyte maturation (2,3). Based on the presence of a CD225 cell growth-regulating protein domain, upregulation of expression by a PPAR γ agonist, and induction of the gene following exit from the mitotic clonal expansion phase of 3T3-L1 adipogenesis, we proposed a working model in which white adipocyte Tusc5 activities are associated with entry into or persistence of the fully mature, growth-arrested metabolic and structural phenotype of adipocytes (1).…”

Section: Introductionmentioning

confidence: 99%

γ-Synuclein Is an Adipocyte-Neuron Gene Coordinately Expressed with Leptin and Increased in Human Obesity , ,3

Oort

Knotts

Grino

et al. 2008

The Journal of Nutrition

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Recently, we characterized tumor suppressor candidate 5 (Tusc5) as an adipocyte-neuron PPARγ target gene. Our objective herein was to identify additional genes that display distinctly high expression in fat and neurons, because such a pattern could signal previously uncharacterized functional pathways shared in these disparate tissues. γ-Synuclein, a marker of peripheral and select central nervous system neurons, was strongly expressed in white adipose tissue (WAT) and peripheral nervous system ganglia using bioinformatics and quantitative PCR approaches. γ-Synuclein expression was determined during adipogenesis and in subcutaneous (SC) and visceral adipose tissue (VAT) from obese and nonobese humans. γ-Synuclein mRNA increased from trace levels in preadipocytes to high levels in mature 3T3-L1 adipocytes and decreased ∼50% following treatment with the PPARγ agonist GW1929 (P < 0.01). Because γ-synuclein limits growth arrest and is implicated in cancer progression in nonadipocytes, we suspected that expression would be increased in situations where WAT plasticity/adipocyte turnover are engaged. Consistent with this postulate, human WAT γ-synuclein mRNA levels consistently increased in obesity and were higher in SC than in VAT; i.e. they increased ∼1.7-fold in obese Pima Indian adipocytes (P = 0.003) and ∼2-fold in SC and VAT of other obese cohorts relative to nonobese subjects. Expression correlated with leptin transcript levels in human SC and VAT (r = 0.887; P < 0.0001; n = 44). γ-Synuclein protein was observed in rodent and human WAT but not in negative control liver. These results are consistent with the hypothesis that γ-synuclein plays an important role in adipocyte physiology.

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Tumor suppressor candidate 5 (TUSC5) is expressed in brown adipocytes

Koide¹,

Shibata²,

Yamada³

et al. 2007

Biochemical and Biophysical Research Communications

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Molecular cloning and characterization of rat brain endothelial cell derived gene-1 (tumor suppressor candidate 5) expressing abundantly in adipose tissues

Cited by 12 publications

References 22 publications

Molecular Characterization of the Tumor Suppressor Candidate 5 Gene: Regulation by PPARγ and Identification of TUSC5 Coding Variants in Lean and Obese Humans

Molecular Characterization of the Tumor Suppressor Candidate 5 Gene: Regulation by PPARγ and Identification of TUSC5 Coding Variants in Lean and Obese Humans

γ-Synuclein Is an Adipocyte-Neuron Gene Coordinately Expressed with Leptin and Increased in Human Obesity , ,3

Tumor suppressor candidate 5 (TUSC5) is expressed in brown adipocytes

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