Epigenetic modifications of the Zfp/ZNF423 gene control murine adipogenic commitment and are dysregulated in human hypertrophic obesity
| Journal Title: | Diabetologia 2017-10-24, Vol.61 (2), p.369-380 |
| Main Author: | Longo, Michele |
| Other Authors: | Raciti, Gregory A , Zatterale, Federica , Parrillo, Luca , Desiderio, Antonella , Spinelli, Rosa , Hammarstedt, Ann , Hedjazifar, Shahram , Hoffmann, Jenny M , Nigro, Cecilia , Mirra, Paola , Fiory, Francesca , Formisano, Pietro , Miele, Claudia , Smith, Ulf , Beguinot, Francesco |
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 Electronic Article
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English |
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| Publisher: | Berlin/Heidelberg: Springer Berlin Heidelberg |
| ID: | ISSN: 0012-186X |
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| recordid: | cdi_swepub_primary_oai_gup_ub_gu_se_260364 |
| title: | Epigenetic modifications of the Zfp/ZNF423 gene control murine adipogenic commitment and are dysregulated in human hypertrophic obesity |
| format: | Article |
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| ispartof: | Diabetologia, 2017-10-24, Vol.61 (2), p.369-380 |
| description: | Aims/hypothesis Subcutaneous adipocyte hypertrophy is associated with insulin resistance and increased risk of type 2 diabetes, and predicts its future development independent of obesity. In humans, subcutaneous adipose tissue hypertrophy is a consequence of impaired adipocyte precursor cell recruitment into the adipogenic pathway rather than a lack of precursor cells. The zinc finger transcription factor known as zinc finger protein (ZFP) 423 has been identified as a major determinant of pre-adipocyte commitment and maintained white adipose cell function. Although its levels do not change during adipogenesis, ectopic expression of Zfp423 in non-adipogenic murine cells is sufficient to activate expression of the gene encoding peroxisome proliferator-activated receptor γ ( Pparγ ; also known as Pparg ) and increase the adipogenic potential of these cells. We investigated whether the Zfp423 gene is under epigenetic regulation and whether this plays a role in the restricted adipogenesis associated with hypertrophic obesity. Methods Murine 3T3-L1 and NIH-3T3 cells were used as fibroblasts committed and uncommitted to the adipocyte lineage, respectively. Human pre-adipocytes were isolated from the stromal vascular fraction of subcutaneous adipose tissue of 20 lean non-diabetic individuals with a wide adipose cell size range. mRNA levels were measured by quantitative real-time PCR, while methylation levels were analysed by bisulphite sequencing. Chromatin structure was analysed by micrococcal nuclease protection assay, and DNA-methyltransferases were chemically inhibited by 5-azacytidine. Adipocyte differentiation rate was evaluated by Oil Red O staining. Results Comparison of uncommitted (NIH-3T3) and committed (3T3-L1) adipose precursor cells revealed that Zfp423 expression increased ( p |
| language: | eng |
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| identifier: | ISSN: 0012-186X |
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