CCAAT/enhancer-binding proteins <i>α</i> and <i>β</i> in brown adipose tissue: evidence for a tissue-specific pattern of expression during development

Manchado, C.; Yubero, Pilar; Viñas, Octavi; Iglesias, Roser; Villarroya, Francesc; Mampel, Teresa; Giralt, Marta

doi:10.1042/bj3020695

Cited by 40 publications

(33 citation statements)

References 47 publications

(75 reference statements)

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“…In addition, there is physiological evidence to support a role for C/EBP␤ in BAT differentiation. Like PGC-1␣ and UCP1, C/EBP␤ (but not C/EBP␣ or -␦) expression in BAT is cold-inducible during cold exposure, adrenergic stimulation, and early development in rodents (37,38,47). Our study on cold-exposed mice clearly demonstrated that the increased expression of Pgc-1␣ and Ucp1 mRNA in iBAT compared with mice maintained at 28°C was accompanied by an increase in C/ebp␤ but not C/ebp␣ or C/ebp␦ mRNA.…”

Section: Discussionmentioning

confidence: 99%

“…Similar to Pgc-1␣ and Ucp1, levels of C/ebp␤ mRNA were highest in iBAT, and responses to the cold environment were rapidly reversed by 24-h reacclimatization in the warmth. Exposure to cold has previously been reported to increase C/ebp␤ but not C/ebp␣ or C/ebp␦ in iBAT (37,38), indicating a positive association of C/EBP␤ gene expression with Pgc-1␣ and Ucp1. We next assessed the levels of Chop10, which has been reported to act as a dominant negative transcription factor of C/EBPs (Fig.…”

Section: Differential Regulation Of C/ebp Isoforms In Brown and Whitementioning

confidence: 99%

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Combinatorial Transcription Factor Regulation of the Cyclic AMP-response Element on the Pgc-1α Promoter in White 3T3-L1 and Brown HIB-1B Preadipocytes

Karamitri

Shore

Docherty

et al. 2009

Journal of Biological Chemistry

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Cold stress in rodents increases the expression of UCP1 and PGC-1␣ in brown and white adipose tissue. We have previously reported that C/EBP␤ specifically binds to the CRE on the proximal Pgc-1␣ promoter and increases forskolin-sensitive Pgc-1␣ and Ucp1 expression in white 3T3-L1 preadipocytes. Here we show that in mice exposed to a cold environment for 24 h, Pgc-1␣, Ucp1, and C/ebp␤ but not C/ebp␣ or C/ebp␦ expression were increased in BAT. Conversely, expression of the C/EBP dominant negative Chop10 was increased in WAT but not BAT during cold exposure. Reacclimatization of cold-exposed mice to a warm environment for 24 h completely reversed these changes in gene expression. In HIB-1B, brown preadipocytes, forskolin increased expression of Pgc-1␣, Ucp1, and C/ebp␤ early in differentiation and inhibited Chop10 expression. Employing chromatin immunoprecipitation, we demonstrate that C/EBP␤, CREB, ATF-2, and CHOP10 are bound to the Pgc-1␣ proximal CRE, but CHOP10 does not bind in HIB-1B cell lysates. Forskolin stimulation and C/EBP␤ overexpression in 3T3-L1 cells increased C/EBP␤ and CREB but displaced ATF-2 and CHOP10 binding to the Pgc-1␣ proximal CRE. Overexpression of ATF-2 and CHOP10 in 3T3-L1 cells decreased Pgc-1␣ transcription. Knockdown of Chop10 in 3T3-L1 cells using siRNA increased Pgc-1␣ transcription, whereas siRNA against C/ebp␤ in HIB-1B cells decreased Pgc-1␣ and Ucp1 expression. We conclude that the increased cAMP stimulation of Pgc-1␣ expression is regulated by the combinatorial effect of transcription factors acting at the CRE on the proximal Pgc-1␣ promoter.

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Section: Discussionmentioning

confidence: 99%

Section: Differential Regulation Of C/ebp Isoforms In Brown and Whitementioning

confidence: 99%

Combinatorial Transcription Factor Regulation of the Cyclic AMP-response Element on the Pgc-1α Promoter in White 3T3-L1 and Brown HIB-1B Preadipocytes

Karamitri

Shore

Docherty

et al. 2009

Journal of Biological Chemistry

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“…To study brown adipose tissue development during the perinatal stage, male and female A/J or B6 mice were mated, and the day of conception was determined by the presence of a vaginal plug. iBAT was collected from fetuses after 18-20 days of gestation, newborn pups (0 h), and 24 h old pups (24). Male mice with ages ranging from 5 days to 4 months were euthanized by cervical dislocation, and iBAT and RP were removed for various measurements.…”

Section: Animalsmentioning

confidence: 99%

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

248

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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“…shows an increase in brown adipocyte-like cells characterized by cAMP accumulation, enhanced mitochondrial biogenesis, and UCP1 expression in WATs (8). In addition, several transcription-related molecules such as retinoblastoma protein (Rb), p107, transcriptional intermediary factor 2, 4E-binding protein 1, and RIP140 (9-15) have been reported to influence the brown or white fat phenotype selectivity.…”

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confidence: 99%

Tuberous Sclerosis Complex 1–Mechanistic Target of Rapamycin Complex 1 Signaling Determines Brown-to-White Adipocyte Phenotypic Switch

Xiang

Tang

et al. 2014

Diabetes

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Interconversion of white and brown adipocytes occurs between anabolic and catabolic states. The molecular mechanism regulating this phenotypic switch remains largely unknown. This study explores the role of tuberous sclerosis complex 1 (TSC1)–mechanistic target of rapamycin (mTOR) signaling in the conversion of brown to white adipose tissue (WAT). A colony of Fabp4-Tsc1−/− mice, in which the Tsc1 gene was specifically deleted by the fatty acid binding protein 4 (FABP4)-Cre, was established. Western blotting and immunostaining demonstrated the absence of TSC1 and activation of ribosomal protein S6 kinase 1, the downstream target of mTOR complex 1 (mTORC1) signaling, in the brown adipose tissues (BATs) of Fabp4-Tsc1−/− mice. Accumulation of lipid droplets in BAT was significantly increased. Levels of brown adipocyte markers were markedly downregulated, while white adipocyte markers were upregulated. Rapamycin reversed the conversion from BAT to WAT in Fabp4-Tsc1−/− mice. Deletion of the Tsc1 gene in cultured brown preadipocytes significantly increased the conversion to white adipocytes. FoxC2 mRNA, the transcriptional factor for brown adipocyte determination, was significantly decreased, while mRNAs for retinoblastoma protein, p107 and RIP140, the transcriptional factors for white adipocyte determination, increased in the BAT of Fabp4-Tsc1−/− mice. Our study demonstrates that TSC1-mTORC1 signaling contributes to the brown-to-white adipocyte phenotypic switch.

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CCAAT/enhancer-binding proteins α and β in brown adipose tissue: evidence for a tissue-specific pattern of expression during development

Cited by 40 publications

References 47 publications

Combinatorial Transcription Factor Regulation of the Cyclic AMP-response Element on the Pgc-1α Promoter in White 3T3-L1 and Brown HIB-1B Preadipocytes

Combinatorial Transcription Factor Regulation of the Cyclic AMP-response Element on the Pgc-1α Promoter in White 3T3-L1 and Brown HIB-1B Preadipocytes

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

Tuberous Sclerosis Complex 1–Mechanistic Target of Rapamycin Complex 1 Signaling Determines Brown-to-White Adipocyte Phenotypic Switch

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