Epigenetic modifications of the Zfp/ZNF423 gene control murine adipogenic commitment and are dysregulated in human hypertrophic obesity
Autor: | Longo M, RACITI GA, Zatterale F, Parrillo L, DESIDERIO, ANTONELLA, Spinelli R, Hammarstedt A, Hedjazifar S, Hoffmann JM, Nigro C, Mirra P, Fiory F, Formisano P, Miele C, Smith U, Beguinot F, LM and RGA contributed equally to this work. |
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Přispěvatelé: | Longo, M, Raciti, Ga, Zatterale, F, Parrillo, L, Desiderio, Antonella, Spinelli, R, Hammarstedt, A, Hedjazifar, S, Hoffmann, Jm, Nigro, C, Mirra, P, Fiory, F, Formisano, P, Miele, C, Smith, U, Beguinot, F, LM and RGA contributed equally to this, Work. |
Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
medicine.medical_specialty Cellular differentiation Endocrinology Diabetes and Metabolism Adipose tissue Basic science Bone Morphogenetic Protein 4 Biology Article Epigenetic regulation Epigenesis Genetic 03 medical and health sciences chemistry.chemical_compound Mice Pathogenic mechanism Adipocyte Internal medicine 3T3-L1 Cells medicine Internal Medicine Transcription factors Adipocytes Animals Humans Adipose tissue differentiation Obesity RNA Messenger Promoter Regions Genetic Weight regulation and obesity Regulation of gene expression DNA methylation Adipogenesis Insulin sensitivity and resistance Cell Differentiation Stromal vascular fraction DNA-Binding Proteins Pathogenic mechanisms 030104 developmental biology Endocrinology chemistry Diabetes Mellitus Type 2 Gene Expression Regulation NIH 3T3 Cells Adipocyte hypertrophy Transcription factor Human |
Zdroj: | Diabetologia Diabetologia (Berl.) 61 (2018): 369–380. doi:10.1007/s00125-017-4471-4 info:cnr-pdr/source/autori:Longo M.; Raciti G.A.; Zatterale F.; Parrillo L.; Desiderio A.; Spinelli R.; Hammarstedt A.; Hedjazifar S.; Hoffmann J.M.; Nigro C.; Mirra P.; Fiory F.; Formisano P.; Miele C.; Smith U.; Beguinot F./titolo:Epigenetic modifications of the Zfp%2FZNF423 gene control murine adipogenic commitment and are dysregulated in human hypertrophic obesity/doi:10.1007%2Fs00125-017-4471-4/rivista:Diabetologia (Berl.)/anno:2018/pagina_da:369/pagina_a:380/intervallo_pagine:369–380/volume:61 |
ISSN: | 1432-0428 0012-186X |
Popis: | 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 |
Databáze: | OpenAIRE |
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