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PPARGC1A Gene Promoter Methylation as a Biomarker of Insulin Secretion and Sensitivity in Response to Glucose Challenges

Santos, José L ; Krause, Bernardo J ; Cataldo, Luis Rodrigo LU orcid ; Vega, Javier ; Salas-Pérez, Francisca ; Mennickent, Paula ; Gallegos, Raúl ; Milagro, Fermín I ; Prieto-Hontoria, Pedro and Riezu-Boj, J Ignacio , et al. (2020) In Nutrients 12(9). p.1-15
Abstract

Methylation in CpG sites of the PPARGC1A gene (encoding PGC1-α) has been associated with adiposity, insulin secretion/sensitivity indexes and type 2 diabetes. We assessed the association between the methylation profile of the PPARGC1A gene promoter gene in leukocytes with insulin secretion/sensitivity indexes in normoglycemic women. A standard oral glucose tolerance test (OGTT) and an abbreviated version of the intravenous glucose tolerance test (IVGTT) were carried out in n = 57 Chilean nondiabetic women with measurements of plasma glucose, insulin, and C-peptide. Bisulfite-treated DNA from leukocytes was evaluated for methylation levels in six CpG sites of the proximal promoter of the PPARGC1A gene by pyrosequencing (positions -816,... (More)

Methylation in CpG sites of the PPARGC1A gene (encoding PGC1-α) has been associated with adiposity, insulin secretion/sensitivity indexes and type 2 diabetes. We assessed the association between the methylation profile of the PPARGC1A gene promoter gene in leukocytes with insulin secretion/sensitivity indexes in normoglycemic women. A standard oral glucose tolerance test (OGTT) and an abbreviated version of the intravenous glucose tolerance test (IVGTT) were carried out in n = 57 Chilean nondiabetic women with measurements of plasma glucose, insulin, and C-peptide. Bisulfite-treated DNA from leukocytes was evaluated for methylation levels in six CpG sites of the proximal promoter of the PPARGC1A gene by pyrosequencing (positions -816, -783, -652, -617, -521 and -515). A strong correlation between the DNA methylation percentage of different CpG sites of the PPARGC1A promoter in leukocytes was found, suggesting an integrated epigenetic control of this region. We found a positive association between the methylation levels of the CpG site -783 with the insulin sensitivity Matsuda composite index (rho = 0.31; p = 0.02) derived from the OGTT. The CpG hypomethylation in the promoter position -783 of the PPARGC1A gene in leukocytes may represent a biomarker of reduced insulin sensitivity after the ingestion of glucose.

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publishing date
type
Contribution to journal
publication status
published
keywords
Adult, Biomarkers/blood, Blood Glucose, Chile, DNA Methylation/genetics, Female, Humans, Insulin Resistance/genetics, Insulin Secretion/genetics, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics, Promoter Regions, Genetic/genetics
in
Nutrients
volume
12
issue
9
article number
2790
pages
1 - 15
publisher
MDPI AG
external identifiers
  • pmid:32933059
  • scopus:85090659603
ISSN
2072-6643
DOI
10.3390/nu12092790
language
English
LU publication?
no
id
b87b1763-8f3a-4c92-ac7a-8ce7f88055df
date added to LUP
2022-02-01 07:36:57
date last changed
2024-05-03 20:36:25
@article{b87b1763-8f3a-4c92-ac7a-8ce7f88055df,
  abstract     = {{<p>Methylation in CpG sites of the PPARGC1A gene (encoding PGC1-α) has been associated with adiposity, insulin secretion/sensitivity indexes and type 2 diabetes. We assessed the association between the methylation profile of the PPARGC1A gene promoter gene in leukocytes with insulin secretion/sensitivity indexes in normoglycemic women. A standard oral glucose tolerance test (OGTT) and an abbreviated version of the intravenous glucose tolerance test (IVGTT) were carried out in n = 57 Chilean nondiabetic women with measurements of plasma glucose, insulin, and C-peptide. Bisulfite-treated DNA from leukocytes was evaluated for methylation levels in six CpG sites of the proximal promoter of the PPARGC1A gene by pyrosequencing (positions -816, -783, -652, -617, -521 and -515). A strong correlation between the DNA methylation percentage of different CpG sites of the PPARGC1A promoter in leukocytes was found, suggesting an integrated epigenetic control of this region. We found a positive association between the methylation levels of the CpG site -783 with the insulin sensitivity Matsuda composite index (rho = 0.31; p = 0.02) derived from the OGTT. The CpG hypomethylation in the promoter position -783 of the PPARGC1A gene in leukocytes may represent a biomarker of reduced insulin sensitivity after the ingestion of glucose.</p>}},
  author       = {{Santos, José L and Krause, Bernardo J and Cataldo, Luis Rodrigo and Vega, Javier and Salas-Pérez, Francisca and Mennickent, Paula and Gallegos, Raúl and Milagro, Fermín I and Prieto-Hontoria, Pedro and Riezu-Boj, J Ignacio and Bravo, Carolina and Salas-Huetos, Albert and Arpón, Ana and Galgani, José E and Martínez, J Alfredo}},
  issn         = {{2072-6643}},
  keywords     = {{Adult; Biomarkers/blood; Blood Glucose; Chile; DNA Methylation/genetics; Female; Humans; Insulin Resistance/genetics; Insulin Secretion/genetics; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics; Promoter Regions, Genetic/genetics}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{1--15}},
  publisher    = {{MDPI AG}},
  series       = {{Nutrients}},
  title        = {{PPARGC1A Gene Promoter Methylation as a Biomarker of Insulin Secretion and Sensitivity in Response to Glucose Challenges}},
  url          = {{http://dx.doi.org/10.3390/nu12092790}},
  doi          = {{10.3390/nu12092790}},
  volume       = {{12}},
  year         = {{2020}},
}