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Open AccessArticle

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

1
Department of Nutrition, Diabetes and Metabolism, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 8331150, Chile
2
Instituto de Ciencias de la Salud, Universidad de O’Higgins, Avenida Libertador Bernardo O’Higgins 611, Rancagua 2841935, Chile
3
Department of Nutrition, Food Sciences and Physiology, Centre for Nutrition Research, University of Navarra, 31008 Pamplona, Spain
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Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, 28029 Madrid, Spain
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IdiSNA, Navarra’s Health Research Institute, 31008 Pamplona, Spain
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Facultad de Ciencias de la Salud, Universidad SEK, Santiago 8340363, Chile
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Andrology and IVF Laboratory, Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT 84108, USA
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Departamento de Ciencias de la Salud, Nutrición y Dietética, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago 781000, Chile
9
IMDEA-Food, 28049 Madrid, Spain
*
Author to whom correspondence should be addressed.
Nutrients 2020, 12(9), 2790; https://doi.org/10.3390/nu12092790
Received: 2 August 2020 / Revised: 28 August 2020 / Accepted: 31 August 2020 / Published: 11 September 2020
(This article belongs to the Special Issue Dietary Biomarkers in Human Nutrition)
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. View Full-Text
Keywords: methylation; insulin sensitivity; insulin secretion; biomarker; gene variant; PPARGC1A gene methylation; insulin sensitivity; insulin secretion; biomarker; gene variant; PPARGC1A gene
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Santos, J.L.; Krause, B.J.; Cataldo, L.R.; Vega, J.; Salas-Pérez, F.; Mennickent, P.; Gallegos, R.; Milagro, F.I.; Prieto-Hontoria, P.; Riezu-Boj, J.I.; Bravo, C.; Salas-Huetos, A.; Arpón, A.; Galgani, J.E.; Martínez, J.A. PPARGC1A Gene Promoter Methylation as a Biomarker of Insulin Secretion and Sensitivity in Response to Glucose Challenges. Nutrients 2020, 12, 2790.

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