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Epigenetic modifications of the Zfp/ZNF423 gene control murine adipogenic commitment and are dysregulated in human hypertrophic obesity

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 recruit... Full description

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
Format: Electronic Article Electronic Article
Language: English
Subjects:
DNA
Publisher: Berlin/Heidelberg: Springer Berlin Heidelberg
ID: ISSN: 0012-186X
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title: Epigenetic modifications of the Zfp/ZNF423 gene control murine adipogenic commitment and are dysregulated in human hypertrophic obesity
format: Article
creator:
  • Longo, Michele
  • 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
subjects:
  • 3T3-L1 Cells
  • Adipocytes
  • Adipocytes - cytology
  • Adipocytes - metabolism
  • Adipogenesis
  • Adipogenesis - genetics
  • Adipogenesis - physiology
  • Adipose tissue
  • Adipose tissue differentiation
  • Animals
  • Article
  • Azacytidine
  • Basic science
  • Bone morphogenetic protein 4
  • Bone Morphogenetic Protein 4 - genetics
  • Bone Morphogenetic Protein 4 - metabolism
  • Cell and Molecular Biology
  • Cell Differentiation - genetics
  • Cell Differentiation - physiology
  • Cell size
  • Cell- och molekylärbiologi
  • Chromatin
  • CpG islands
  • Deoxyribonucleic acid
  • Diabetes mellitus
  • Diabetes Mellitus, Type 2 - genetics
  • Diabetes Mellitus, Type 2 - metabolism
  • DNA
  • DNA binding proteins
  • DNA methylation
  • DNA Methylation - genetics
  • DNA Methylation - physiology
  • DNA sequencing
  • DNA-Binding Proteins - genetics
  • DNA-Binding Proteins - metabolism
  • Ectopic expression
  • Epigenesis, Genetic - genetics
  • Epigenetic inheritance
  • Epigenetic regulation
  • Epigenetics
  • Fibroblasts
  • Gene Expression Regulation - genetics
  • Gene Expression Regulation - physiology
  • Genes
  • Genetic research
  • Human
  • Human Physiology
  • Humans
  • Hypertrophy
  • Insulin
  • Insulin resistance
  • Insulin sensitivity
  • Insulin sensitivity and resistance
  • Internal Medicine
  • Medicine
  • Medicine & Public Health
  • Metabolic Diseases
  • Methylation
  • Methyltransferases
  • Mice
  • NIH 3T3 Cells
  • Nuclease
  • Obesity
  • Obesity - genetics
  • Obesity - metabolism
  • Pathogenic mechanisms
  • Peroxisome proliferator-activated receptors
  • Promoter Regions, Genetic - genetics
  • resistance
  • RNA, Messenger - genetics
  • RNA, Messenger - metabolism
  • Transcription factors
  • Transcription Factors - genetics
  • Transcription Factors - metabolism
  • Type 2 diabetes
  • Weight regulation
  • Weight regulation and obesity
  • Zinc finger proteins
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
source:
identifier: ISSN: 0012-186X
fulltext: no_fulltext
issn:
  • 0012-186X
  • 1432-0428
  • 1432-0428
url: Link


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titleEpigenetic modifications of the Zfp/ZNF423 gene control murine adipogenic commitment and are dysregulated in human hypertrophic obesity
creatorLongo, Michele ; 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
creatorcontribLongo, Michele ; 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 ; Sahlgrenska akademin ; Institute of Medicine, Department of Molecular and Clinical Medicine ; Institutionen för medicin, avdelningen för molekylär och klinisk medicin ; Göteborgs universitet ; Gothenburg University ; Sahlgrenska Academy
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1ISSN: 1432-0428
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languageeng
publisherBerlin/Heidelberg: Springer Berlin Heidelberg
subject3T3-L1 Cells ; Adipocytes ; Adipocytes - cytology ; Adipocytes - metabolism ; Adipogenesis ; Adipogenesis - genetics ; Adipogenesis - physiology ; Adipose tissue ; Adipose tissue differentiation ; Animals ; Article ; Azacytidine ; Basic science ; Bone morphogenetic protein 4 ; Bone Morphogenetic Protein 4 - genetics ; Bone Morphogenetic Protein 4 - metabolism ; Cell and Molecular Biology ; Cell Differentiation - genetics ; Cell Differentiation - physiology ; Cell size ; Cell- och molekylärbiologi ; Chromatin ; CpG islands ; Deoxyribonucleic acid ; Diabetes mellitus ; Diabetes Mellitus, Type 2 - genetics ; Diabetes Mellitus, Type 2 - metabolism ; DNA ; DNA binding proteins ; DNA methylation ; DNA Methylation - genetics ; DNA Methylation - physiology ; DNA sequencing ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; Ectopic expression ; Epigenesis, Genetic - genetics ; Epigenetic inheritance ; Epigenetic regulation ; Epigenetics ; Fibroblasts ; Gene Expression Regulation - genetics ; Gene Expression Regulation - physiology ; Genes ; Genetic research ; Human ; Human Physiology ; Humans ; Hypertrophy ; Insulin ; Insulin resistance ; Insulin sensitivity ; Insulin sensitivity and resistance ; Internal Medicine ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Methylation ; Methyltransferases ; Mice ; NIH 3T3 Cells ; Nuclease ; Obesity ; Obesity - genetics ; Obesity - metabolism ; Pathogenic mechanisms ; Peroxisome proliferator-activated receptors ; Promoter Regions, Genetic - genetics ; resistance ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Transcription factors ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Type 2 diabetes ; Weight regulation ; Weight regulation and obesity ; Zinc finger proteins
ispartofDiabetologia, 2017-10-24, Vol.61 (2), p.369-380
rights
0The Author(s) 2017
1COPYRIGHT 2018 Springer
2Diabetologia is a copyright of Springer, (2017). All Rights Reserved.
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0Longo, Michele
1Raciti, Gregory A
2Zatterale, Federica
3Parrillo, Luca
4Desiderio, Antonella
5Spinelli, Rosa
6Hammarstedt, Ann
7Hedjazifar, Shahram
8Hoffmann, Jenny M
9Nigro, Cecilia
10Mirra, Paola
11Fiory, Francesca
12Formisano, Pietro
13Miele, Claudia
14Smith, Ulf
15Beguinot, Francesco
16Sahlgrenska akademin
17Institute of Medicine, Department of Molecular and Clinical Medicine
18Institutionen för medicin, avdelningen för molekylär och klinisk medicin
19Göteborgs universitet
20Gothenburg University
21Sahlgrenska Academy
title
0Epigenetic modifications of the Zfp/ZNF423 gene control murine adipogenic commitment and are dysregulated in human hypertrophic obesity
1Diabetologia
addtitle
0Diabetologia
1Diabetologia
description
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03T3-L1 Cells
1Adipocytes
2Adipocytes - cytology
3Adipocytes - metabolism
4Adipogenesis
5Adipogenesis - genetics
6Adipogenesis - physiology
7Adipose tissue
8Adipose tissue differentiation
9Animals
10Article
11Azacytidine
12Basic science
13Bone morphogenetic protein 4
14Bone Morphogenetic Protein 4 - genetics
15Bone Morphogenetic Protein 4 - metabolism
16Cell and Molecular Biology
17Cell Differentiation - genetics
18Cell Differentiation - physiology
19Cell size
20Cell- och molekylärbiologi
21Chromatin
22CpG islands
23Deoxyribonucleic acid
24Diabetes mellitus
25Diabetes Mellitus, Type 2 - genetics
26Diabetes Mellitus, Type 2 - metabolism
27DNA
28DNA binding proteins
29DNA methylation
30DNA Methylation - genetics
31DNA Methylation - physiology
32DNA sequencing
33DNA-Binding Proteins - genetics
34DNA-Binding Proteins - metabolism
35Ectopic expression
36Epigenesis, Genetic - genetics
37Epigenetic inheritance
38Epigenetic regulation
39Epigenetics
40Fibroblasts
41Gene Expression Regulation - genetics
42Gene Expression Regulation - physiology
43Genes
44Genetic research
45Human
46Human Physiology
47Humans
48Hypertrophy
49Insulin
50Insulin resistance
51Insulin sensitivity
52Insulin sensitivity and resistance
53Internal Medicine
54Medicine
55Medicine & Public Health
56Metabolic Diseases
57Methylation
58Methyltransferases
59Mice
60NIH 3T3 Cells
61Nuclease
62Obesity
63Obesity - genetics
64Obesity - metabolism
65Pathogenic mechanisms
66Peroxisome proliferator-activated receptors
67Promoter Regions, Genetic - genetics
68resistance
69RNA, Messenger - genetics
70RNA, Messenger - metabolism
71Transcription factors
72Transcription Factors - genetics
73Transcription Factors - metabolism
74Type 2 diabetes
75Weight regulation
76Weight regulation and obesity
77Zinc finger proteins
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1Raciti, Gregory A
2Zatterale, Federica
3Parrillo, Luca
4Desiderio, Antonella
5Spinelli, Rosa
6Hammarstedt, Ann
7Hedjazifar, Shahram
8Hoffmann, Jenny M
9Nigro, Cecilia
10Mirra, Paola
11Fiory, Francesca
12Formisano, Pietro
13Miele, Claudia
14Smith, Ulf
15Beguinot, Francesco
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titleEpigenetic modifications of the Zfp/ZNF423 gene control murine adipogenic commitment and are dysregulated in human hypertrophic obesity
authorLongo, Michele ; 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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topic
03T3-L1 Cells
1Adipocytes
2Adipocytes - cytology
3Adipocytes - metabolism
4Adipogenesis
5Adipogenesis - genetics
6Adipogenesis - physiology
7Adipose tissue
8Adipose tissue differentiation
9Animals
10Article
11Azacytidine
12Basic science
13Bone morphogenetic protein 4
14Bone Morphogenetic Protein 4 - genetics
15Bone Morphogenetic Protein 4 - metabolism
16Cell and Molecular Biology
17Cell Differentiation - genetics
18Cell Differentiation - physiology
19Cell size
20Cell- och molekylärbiologi
21Chromatin
22CpG islands
23Deoxyribonucleic acid
24Diabetes mellitus
25Diabetes Mellitus, Type 2 - genetics
26Diabetes Mellitus, Type 2 - metabolism
27DNA
28DNA binding proteins
29DNA methylation
30DNA Methylation - genetics
31DNA Methylation - physiology
32DNA sequencing
33DNA-Binding Proteins - genetics
34DNA-Binding Proteins - metabolism
35Ectopic expression
36Epigenesis, Genetic - genetics
37Epigenetic inheritance
38Epigenetic regulation
39Epigenetics
40Fibroblasts
41Gene Expression Regulation - genetics
42Gene Expression Regulation - physiology
43Genes
44Genetic research
45Human
46Human Physiology
47Humans
48Hypertrophy
49Insulin
50Insulin resistance
51Insulin sensitivity
52Insulin sensitivity and resistance
53Internal Medicine
54Medicine
55Medicine & Public Health
56Metabolic Diseases
57Methylation
58Methyltransferases
59Mice
60NIH 3T3 Cells
61Nuclease
62Obesity
63Obesity - genetics
64Obesity - metabolism
65Pathogenic mechanisms
66Peroxisome proliferator-activated receptors
67Promoter Regions, Genetic - genetics
68resistance
69RNA, Messenger - genetics
70RNA, Messenger - metabolism
71Transcription factors
72Transcription Factors - genetics
73Transcription Factors - metabolism
74Type 2 diabetes
75Weight regulation
76Weight regulation and obesity
77Zinc finger proteins
toplevelpeer_reviewed
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0Longo, Michele
1Raciti, Gregory A
2Zatterale, Federica
3Parrillo, Luca
4Desiderio, Antonella
5Spinelli, Rosa
6Hammarstedt, Ann
7Hedjazifar, Shahram
8Hoffmann, Jenny M
9Nigro, Cecilia
10Mirra, Paola
11Fiory, Francesca
12Formisano, Pietro
13Miele, Claudia
14Smith, Ulf
15Beguinot, Francesco
16Sahlgrenska akademin
17Institute of Medicine, Department of Molecular and Clinical Medicine
18Institutionen för medicin, avdelningen för molekylär och klinisk medicin
19Göteborgs universitet
20Gothenburg University
21Sahlgrenska Academy
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0Longo, Michele
1Raciti, Gregory A
2Zatterale, Federica
3Parrillo, Luca
4Desiderio, Antonella
5Spinelli, Rosa
6Hammarstedt, Ann
7Hedjazifar, Shahram
8Hoffmann, Jenny M
9Nigro, Cecilia
10Mirra, Paola
11Fiory, Francesca
12Formisano, Pietro
13Miele, Claudia
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atitleEpigenetic modifications of the Zfp/ZNF423 gene control murine adipogenic commitment and are dysregulated in human hypertrophic obesity
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11432-0428
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