Sequestration of Thermogenic Transcription Factors in the Cytoplasm during Development of Brown Adipose Tissue

Rim, Jong S.; Xue, Bingzhong; Gawrońska‐Kozak, Barbara; Kozak, Leslie P.

doi:10.1074/jbc.m402102200

Cited by 42 publications

(42 citation statements)

References 68 publications

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“…2C). These patterns of brown adipocyte expression are consistent with those observed by others (24,(29)(30)(31)(32) and with previously published results from our laboratory with B6 mice (33). No strain-dependent variations in either Ucp1 expression or mitochondrial amount in iBAT were detected between A/J and B6 mice from 18 days of gestation to 4 months of age.…”

Section: Induction Of Ucp1 Expression In Ibat During Developmentsupporting

confidence: 81%

Genetic variability affects the development of brown adipocytes in white fat but not in interscapular brown fat

Xue¹,

Rim

Hogan

et al. 2007

Journal of Lipid Research

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228

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Cold exposure induces brown adipocytes in retroperitoneal fat (RP) of adult A/J mice but not in C57BL/6J (B6) mice. In contrast, induction of the mitochondrial uncoupling protein 1 gene (Ucp1) in interscapular brown adipose tissue (iBAT) shows no strain dependence. We now show that unlike iBAT, in which Ucp1 was expressed in the fetus and continued throughout life, in RP, Ucp1 was transiently expressed between 10 and 30 days of age and then disappeared. Similar to the lack of genetic variation in the expression of Ucp1 in iBAT during cold induction of adult mice, no genetic variation in Ucp1 expression in iBAT was detected during development. In contrast, UCP1-positive multilocular adipocytes, together with corresponding increases in Ucp1 expression, appeared in RP at 10 days of age in A/J and B6 mice, but with much higher expression in A/J mice. At 20 days of age, brown adipocytes represent the major adipocyte present in RP of A/J mice. The disappearance of brown adipocytes by 30 days of age suggested that tissue remodeling occurred in RP. Genetic variability in Ucp1 expression could not be explained by variation in the expression of selective transcription factors and signaling molecules of adipogenesis. In summary, the existence of genetic variability between A/J and B6 mice during the development of brown adipocyte expression in RP, but not in iBAT, suggests that developmental mechanisms for the brown adipocyte differentiation program are different in these adipose tissues.-Xue, B., J-S. Rim, J. C. Hogan, A. A. Coulter, R. A. Koza, and L. P. Kozak. Genetic variability affects the development of brown adipocytes in white fat but not in interscapular brown fat. J. Lipid Res. 2007. 48: 41-51.

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Section: Induction Of Ucp1 Expression In Ibat During Developmentsupporting

confidence: 81%

Genetic variability affects the development of brown adipocytes in white fat but not in interscapular brown fat

Xue¹,

Rim

Hogan

et al. 2007

Journal of Lipid Research

Self Cite

250

228

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“…C/EBP␤ interaction with other proteins as well as There is physiological evidence to support a role for C/EBP␤ in BAT differentiation. Like PGC-1␣, C/EBP␤ expression in BAT is cold-inducible; during cold exposure, adrenergic stimulation and early development in rodents, C/EBP␤, but not C/EBP␣ or -␦, is increased in BAT but not WAT, in parallel with increases in UCP1 and PGC-1␣ mRNA (26,27). We have confirmed that PGC-1␣, C/EBP␤, and UCP1 mRNA increase in BAT but not WAT of cold-stressed mice (results not shown).…”

Section: Discussionmentioning

confidence: 99%

C/EBPβ Reprograms White 3T3-L1 Preadipocytes to a Brown Adipocyte Pattern of Gene Expression

Karamanlidis

Karamitri

Docherty

et al. 2007

Journal of Biological Chemistry

100

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cAMP-dependent protein kinase induction of PPAR␥ coactivator-1␣ (PGC-1␣) and uncoupling protein 1 (UCP1) expression is an essential step in the commitment of preadipocytes to the brown adipose tissue (BAT) lineage. We studied the molecular mechanisms responsible for differential expression of PGC-1␣ in HIB1B (BAT) and 3T3-L1 white adipose tissue (WAT) precursor cell lines. In HIB1B cells PGC-1␣ and UCP1 expression is cAMP-inducible, but in 3T3-L1 cells, expression is reduced and is cAMP-insensitive. A proximal 264-bp PGC-1␣ reporter construct was cAMP-inducible only in HIB1B cells and was suppressed by site-directed mutagenesis of the proximal cAMP response element (CRE). In electrophoretic mobility shift assays, the transcription factors CREB and C/EBP␤, but not C/EBP␣ and C/EBP␦, bound to the CRE on the PGC-1␣ promoter region in HIB1B and 3T3-L1 cells. Chromatin immunoprecipitation studies demonstrated that C/EBP␤ and CREB bound to the CRE region in HIB1B and 3T3-L1 cell lysates. C/EBP␤ expression was induced by cAMP only in HIB1B cells, and overexpression of C/EBP␤ rescued cAMP-inducible PGC-1␣ and UCP1 expression in 3T3-L1 cells. These data demonstrate that differentiation of preadipocytes toward the BAT rather than the WAT phenotype is controlled in part by the action of C/EBP␤ on the CRE in PGC-1␣ proximal promoter.

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“…3D; both the dominant PPAR␣ isoform and the repressed PPAR␥ isoform are recognized by the antibody). The absence of translocation of PPAR nuclear receptors into the cytoplasm under any of the circumstances studied indicates their active transcriptional role in brown adipocytes (43), as nuclear receptor translocation to the cytoplasm would evidently abolish the ability to control gene expression (52).…”

Section: Resultsmentioning

confidence: 99%

Thermogenically competent nonadrenergic recruitment in brown preadipocytes by a PPARγ agonist

Petrovič

Shabalina²,

Timmons³

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

127

111

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Most physiologically induced examples of recruitment of brown adipose tissue (BAT) occur as a consequence of chronic sympathetic stimulation (norepinephrine release within the tissue). However, in some physiological contexts (e.g., prenatal and prehibernation recruitment), this pathway is functionally contraindicated. Thus a nonsympathetically mediated mechanism of BAT recruitment must exist. Here we have tested whether a PPARγ activation pathway could competently recruit BAT, independently of sympathetic stimulation. We continuously treated primary cultures of mouse brown (pre)adipocytes with the potent peroxisome proliferator-activated receptor-γ (PPARγ) agonist rosiglitazone. In rosiglitazone-treated cultures, morphological signs of adipose differentiation and expression levels of the general adipogenic marker aP2 were manifested much earlier than in control cultures. Importantly, in the presence of the PPARγ agonist the brown adipocyte phenotype was significantly enhanced: UCP1 was expressed even in the absence of norepinephrine, and PPARα expression and norepinephrine-induced PGC-1α mRNA levels were significantly increased. However, the augmented levels of PPARα could not explain the brown-fat promoting effect of rosiglitazone, as this effect was still evident in PPARα-null cells. In continuously rosiglitazone-treated brown adipocytes, mitochondriogenesis, an essential part of BAT recruitment, was significantly enhanced. Most importantly, these mitochondria were capable of thermogenesis, as rosiglitazone-treated brown adipocytes responded to the addition of norepinephrine with a large increase in oxygen consumption. This thermogenic response was not observable in rosiglitazone-treated brown adipocytes originating from UCP1-ablated mice; hence, it was UCP1 dependent. Thus the PPARγ pathway represents an alternative, potent, and fully competent mechanism for BAT recruitment, which may be the cellular explanation for the enigmatic recruitment in prehibernation and prenatal states.

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Sequestration of Thermogenic Transcription Factors in the Cytoplasm during Development of Brown Adipose Tissue

Cited by 42 publications

References 68 publications

Genetic variability affects the development of brown adipocytes in white fat but not in interscapular brown fat

Genetic variability affects the development of brown adipocytes in white fat but not in interscapular brown fat

C/EBPβ Reprograms White 3T3-L1 Preadipocytes to a Brown Adipocyte Pattern of Gene Expression

Thermogenically competent nonadrenergic recruitment in brown preadipocytes by a PPARγ agonist

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