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.
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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