Ectopic expression of the CCAAT/enhancer-binding protein alpha promotes the adipogenic program in a variety of mouse fibroblastic cells.

Freytag, Svend O.; Paielli, Dell; Gilbert, Jeff D.

doi:10.1101/gad.8.14.1654

Cited by 414 publications

(315 citation statements)

References 34 publications

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“…Previous studies have indicated that antisense RNA against the mRNA of C/EBPa suppressed the differentiation of preadipocytes, whereas the ectopic expression of C/EBPa promoted this process. 37,38 It was shown that C/EBPa activated several genes, such as AGT, adipocyte protein-2 and stearoyl-CoA desaturase during preadipocytes differentiation. 36,39 Ang II, uniquely generated from AGT, could stimulate the production and release of prostacyclin, which promotes the process of preadipocytes differentiation subsequently.…”

Section: Agt Knockdown Inhibits Hpa-v Differentiation Z-w Ye Et Almentioning

confidence: 99%

Knockdown of angiotensinogen by shRNA-mediated RNA interference inhibits human visceral preadipocytes differentiation

Jiang

2009

Int J Obes

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Objective: The immediate cause of obesity is the massive deposition of subcutaneous and visceral fat attributing to the continuous proliferation and differentiation of preadipocytes. The identification of the underlying molecular mechanisms of preadipocytes differentiation is urgent, and will have an important role in plastic and reconstructive surgical procedures. Methods: Two small hairpin RNA (shRNA)-mediated RNA interference plasmids have been constructed on the basis of the activity of H1 promoter-driven expression vector psiRNA-hH1neo to suppress the expression of angiotensinogen (AGT) in human preadipocytes-visceral (HPA-v). Subsequently, glycerol-3-phosphate dehydrogenase (G3PDH) activity and intracytoplasmic lipids content were detected during the process of HPA-v differentiation. Results: Small hairpin RNA-expressing vectors have been successfully constructed to suppress the expression of AGT significantly. Both intracytoplasmic lipids content and G3PDH activity decreased to a certain extent compared with that in the control group in the whole process of HPA-v differentiation. Conclusions: Two shRNA-mediated AGT-targeting plasmids inhibited the process of HPA-v differentiation to a certain extent. However, the accumulation of intracytoplasmic lipids was not exclusively determined by the expression of AGT, and it may also be regulated by other factors. In conclusion, this study provided a method to inhibit the process of preadipocytes differentiation, and it may have a role in obesity treatment and adipose tissue engineering application.

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Section: Agt Knockdown Inhibits Hpa-v Differentiation Z-w Ye Et Almentioning

confidence: 99%

Knockdown of angiotensinogen by shRNA-mediated RNA interference inhibits human visceral preadipocytes differentiation

Jiang

2009

Int J Obes

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“…It has been clearly demonstrated that C/EBPalpha is a key player in adipocyte differentiation (Cao et al, 1991;Lin and Lane, 1994;Hu et al, 1995). For example, fibroblasts differentiated into adipocytes following ectopic expression of C/EBPalpha (Freytag et al, 1994;Park et al, 2004). It has also been reported that the C/EBPalphamediated myoblast to adipocyte transition of C2C12 takes place in the absence of adipocyte differentiation medium (Fux et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

FMIP controls the adipocyte lineage commitment of C2C12 cells by downmodulation of C/EBPalpha

et al. 2006

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Fms interacting protein (FMIP) is a substrate for Fms tyrosine kinase, and a nuclear/cytoplasm shuttling protein with a leucine zipper. As the phosphorylation of FMIP is observed in insulin-stimulated preadipocytes, we examined the role of FMIP in adipocyte differentiation, using the mesenchymal multipotent stem cells, C2C12 cells, that can differentiate into adipocytes, muscle cells and osteoblasts. Ectopic expression of FMIP in C2C12 impairs the adipocyte differentiation induced by treatment with insulin, dexamethasone and 3-isobutyl-1-methylxanthine. These cells exhibit muscle phenotype with multinuclear morphology. Furthermore, knockdown of endogenous FMIP expression by small interfering RNA improves adipocytic lineage commitment of C2C12 cells, while impairing muscle differentiation. Upon stimulation with insulin, CCAAT/enhancer binding protein (C/EBP)-beta, but not C/EBPalpha, is upregulated in cells expressing ectopic FMIP, whereas in FMIP knockdown cells, C/EBPalpha is constitutively expressed. Ectopic expression of C/EBPalpha counteracts the effects of FMIP, whereas C/EBPalpha knockdown partially mimics the effects of FMIP in this system. Northern blot analysis and reverse transcriptase-polymerase chain reaction study reveal that ectopic FMIP-expressing cells do not contain the polyadenylated C/EBPalpha mRNA, but contain the C/EBPalpha pre-mRNA, suggesting that FMIP plays a role in RNA processing and/or export. Indeed, a member of the THO complex that plays a role in mRNA export, THOC1, is co-precipitated with FMIP. The data we have acquired on FMIP suggest that it is a target for tyrosine kinase receptors that potentiate mRNA export.

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“…The transcription factor C/EBP␣ has been shown to regulate several biological processes such as adipose differentiation (12,25,37,44), energy metabolism (38), and cell proliferation (9,15,36). The transcriptional regulation of specific genes by C/EBP␣ has been found to be a major mechanism in the control of adipose tissue differentiation and energy metabolism.…”

Section: Discussionmentioning

confidence: 99%

“…C/EBP␣ binds to DNA as homo-or heterodimers with other family members and activates the transcription of target genes (2,21). C/EBP␣ has been shown to play a significant role in adipocyte differentiation (12,25,37) and in the regulation of both liver-and adipocyte-specific genes (13,44). The generation of C/EBP␣ knockout mice showed a central role for C/EBP␣ in energy metabolism (38).…”

mentioning

confidence: 99%

C/EBPα Regulates Formation of S-Phase-Specific E2F-p107 Complexes in Livers of Newborn Mice

Timchenko

Wilde

Darlington

1999

Molecular and Cellular Biology

104

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We previously showed that the rate of hepatocyte proliferation in livers from newborn C/EBP␣ knockout mice was increased. An examination of cell cycle-related proteins showed that the cyclin-dependent kinase (CDK) inhibitor p21 level was reduced in the knockout animals compared to that in wild-type littermates. Here we show additional cell cycle-associated proteins that are affected by C/EBP␣. We have observed that C/EBP␣ controls the composition of E2F complexes through interaction with the retinoblastoma (Rb)-like protein, p107, during prenatal liver development. S-phase-specific E2F complexes containing E2F, DP, cdk2, cyclin A, and p107 are observed in the developing liver. In wild-type animals these complexes disappear by day 18 of gestation and are no longer present in the newborn animals. In the C/EBP␣ mutant, the S-phase-specific complexes do not diminish and persist to birth. The elevation of levels of the S-phase-specific E2F-p107 complexes in C/EBP␣ knockout mice correlates with the increased expression of several E2F-dependent genes such as those that encode cyclin A, proliferating cell nuclear antigen, and p107. The C/EBP␣-mediated regulation of E2F binding is specific, since the deletion of another C/EBP family member, C/EBP␤, does not change the pattern of E2F binding during prenatal liver development. The addition of bacterially expressed, purified His-C/EBP␣ to the E2F binding reaction resulted in the disruption of E2F complexes containing p107 in nuclear extracts from C/EBP␣ knockout mouse livers. Ectopic expression of C/EBP␣ in cultured cells also leads to a reduction of E2F complexes containing Rb family proteins. Coimmunoprecipitation analyses revealed an interaction of C/EBP␣ with p107 but none with cdk2, E2F1, or cyclin A. A region of C/EBP␣ that has sequence similarity to E2F is sufficient for the disruption of the E2F-p107 complexes. Despite its role as a DNA binding protein, C/EBP␣ brings about a change in E2F complex composition through a protein-protein interaction. The disruption of E2F-p107 complexes correlates with C/EBP␣-mediated growth arrest of hepatocytes in newborn animals.

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Ectopic expression of the CCAAT/enhancer-binding protein alpha promotes the adipogenic program in a variety of mouse fibroblastic cells.

Cited by 414 publications

References 34 publications

Knockdown of angiotensinogen by shRNA-mediated RNA interference inhibits human visceral preadipocytes differentiation

Knockdown of angiotensinogen by shRNA-mediated RNA interference inhibits human visceral preadipocytes differentiation

FMIP controls the adipocyte lineage commitment of C2C12 cells by downmodulation of C/EBPalpha

C/EBPα Regulates Formation of S-Phase-Specific E2F-p107 Complexes in Livers of Newborn Mice

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