Aim: First-degree relatives (FDR) of individuals with Type 2 diabetes (T2D) feature restricted adipogenesis, which render them more vulnerable to T2D. Epigenetics may contribute to these abnormalities. Methods: FDR pre-adipocyte Methylome and Transcriptome were investigated by MeDIP- and RNA-Seq, respectively. Results:Methylome analysis revealed 2841 differentially methylated regions (DMR) in FDR. Most DMR localized into gene-body and were hypomethylated. The strongest hypomethylation signal was identified in an intronic-DMR at the PTPRD gene. PTPRD hypomethylation in FDR was confirmed by bisulphite sequencing and was responsible for its upregulation. Interestingly, Ptprd-overexpression in 3T3-L1 pre-adipocytes inhibited adipogenesis. Notably, the validated PTPRD-associated DMR was significantly hypomethylated in peripheral blood leukocytes from the same FDR individuals. Finally, PTPRD methylation pattern was also replicated in obese individuals. Conclusion: Our findings indicated a previously unrecognized role of PTPRD in restraining adipogenesis. This abnormality may contribute to increase FDR proclivity toward T2D.

Altered PTPRD DNA methylation associates with restricted adipogenesis in healthy first-degree relatives of Type 2 diabetes subjects / Parrillo, Luca; Spinelli, Rosa; Longo, Michele; Desiderio, Antonella; Mirra, Paola; Nigro, Cecilia; Fiory, Francesca; Hedjazifar, Shahram; Mutarelli, Margherita; Carissimo, Annamaria; Formisano, Pietro; Miele, Claudia; Smith, Ulf; Raciti, Gregory Alexander; Beguinot, Francesco. - In: EPIGENOMICS. - ISSN 1750-1911. - 12:10(2020), pp. 873-888. [10.2217/epi-2019-0267]

Altered PTPRD DNA methylation associates with restricted adipogenesis in healthy first-degree relatives of Type 2 diabetes subjects

Parrillo, Luca;Spinelli, Rosa;Longo, Michele;Desiderio, Antonella;Fiory, Francesca;Formisano, Pietro;Raciti, Gregory Alexander;Beguinot, Francesco
2020

Abstract

Aim: First-degree relatives (FDR) of individuals with Type 2 diabetes (T2D) feature restricted adipogenesis, which render them more vulnerable to T2D. Epigenetics may contribute to these abnormalities. Methods: FDR pre-adipocyte Methylome and Transcriptome were investigated by MeDIP- and RNA-Seq, respectively. Results:Methylome analysis revealed 2841 differentially methylated regions (DMR) in FDR. Most DMR localized into gene-body and were hypomethylated. The strongest hypomethylation signal was identified in an intronic-DMR at the PTPRD gene. PTPRD hypomethylation in FDR was confirmed by bisulphite sequencing and was responsible for its upregulation. Interestingly, Ptprd-overexpression in 3T3-L1 pre-adipocytes inhibited adipogenesis. Notably, the validated PTPRD-associated DMR was significantly hypomethylated in peripheral blood leukocytes from the same FDR individuals. Finally, PTPRD methylation pattern was also replicated in obese individuals. Conclusion: Our findings indicated a previously unrecognized role of PTPRD in restraining adipogenesis. This abnormality may contribute to increase FDR proclivity toward T2D.
2020
Altered PTPRD DNA methylation associates with restricted adipogenesis in healthy first-degree relatives of Type 2 diabetes subjects / Parrillo, Luca; Spinelli, Rosa; Longo, Michele; Desiderio, Antonella; Mirra, Paola; Nigro, Cecilia; Fiory, Francesca; Hedjazifar, Shahram; Mutarelli, Margherita; Carissimo, Annamaria; Formisano, Pietro; Miele, Claudia; Smith, Ulf; Raciti, Gregory Alexander; Beguinot, Francesco. - In: EPIGENOMICS. - ISSN 1750-1911. - 12:10(2020), pp. 873-888. [10.2217/epi-2019-0267]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/809073
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 12
  • ???jsp.display-item.citation.isi??? 11
social impact