Leptin Gene Epigenetic Adaptation to Impaired Glucose Metabolism During Pregnancy
| Autor: | Julie St-Pierre, Alexandre Monpetit, Marta Santuré, Simon-Pierre Guay, Stéphanie Thibault, Diane Brisson, Patrice Perron, Luigi Bouchard |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Leptin medicine.medical_specialty Endocrinology Diabetes and Metabolism Adipokine 030209 endocrinology & metabolism Type 2 diabetes Impaired glucose tolerance 03 medical and health sciences 0302 clinical medicine Pregnancy Diabetes mellitus Internal medicine Glucose Intolerance Internal Medicine Humans Medicine Epigenetics Pathophysiology/Complications Original Research 030304 developmental biology Advanced and Specialized Nursing 0303 health sciences Glucose tolerance test medicine.diagnostic_test Reverse Transcriptase Polymerase Chain Reaction business.industry DNA Methylation Glucose Tolerance Test medicine.disease Endocrinology DNA methylation Female business hormones hormone substitutes and hormone antagonists |
| Zdroj: | Diabetes Care |
| ISSN: | 1935-5548 0149-5992 |
| DOI: | 10.2337/dc10-1024 |
| Popis: | OBJECTIVE To verify whether the leptin gene epigenetic (DNA methylation) profile is altered in the offspring of mothers with gestational impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS Placental tissues and maternal and cord blood samples were obtained from 48 women at term including 23 subjects with gestational IGT. Leptin DNA methylation, gene expression levels, and circulating concentration were measured using the Sequenom EpiTYPER system, quantitative real-time RT-PCR, and enzyme-linked immunosorbent assay, respectively. IGT was assessed after a 75-g oral glucose tolerance test (OGTT) at 24–28 weeks of gestation. RESULTS We have shown that placental leptin gene DNA methylation levels were correlated with glucose levels (2-h post-OGTT) in women with IGT (fetal side: ρ = −0.44, P ≤ 0.05; maternal side: ρ = 0.53, P ≤ 0.01) and with decreased leptin gene expression (n = 48; ρ ≥ −0.30, P ≤ 0.05) in the whole cohort. Placental leptin mRNA levels accounted for 16% of the variance in maternal circulating leptin concentration (P < 0.05). CONCLUSIONS IGT during pregnancy was associated with leptin gene DNA methylation adaptations with potential functional impacts. These epigenetic changes provide novel mechanisms that could contribute to explaining the detrimental health effects associated with fetal programming, such as long-term increased risk of developing obesity and type 2 diabetes. |
| Databáze: | OpenAIRE |
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