Differential adipokine DNA methylation and gene expression in subcutaneous adipose tissue from adult offspring of women with diabetes in pregnancy

被引:51
作者
Houshmand-Oeregaard, Azadeh [1 ,2 ,3 ]
Hansen, Ninna S. [2 ,3 ,4 ]
Hjort, Line [2 ,3 ,4 ]
Kelstrup, Louise [1 ,3 ]
Broholm, Christa [2 ]
Mathiesen, Elisabeth R. [1 ,3 ,5 ]
Clausen, Tine D. [3 ,6 ]
Damm, Peter [1 ,3 ]
Vaag, Allan [2 ,3 ,7 ]
机构
[1] Ctr Pregnant Women Diabet, Dept Obstet Rigshospitalet, Dept 7821, Blegdamsvej 9, DK-2100 Copenhagen, Denmark
[2] Rigshospitalet, Dept Endocrinol, Diabetes & Metab, Copenhagen, Denmark
[3] Univ Copenhagen, Fac Hlth & Med Sci, Inst Clin Med, Copenhagen, Denmark
[4] Danish Diabet Acad, Danish PhD Sch Mol Metab, Odense, Denmark
[5] Rigshospitalet, Ctr Pregnant Women Diabet, Dept Endocrinol, Copenhagen, Denmark
[6] Univ Copenhagen, Nordsjaellands Hosp, Dept Obstet & Gynaecol, Hillerod, Denmark
[7] AstraZeneca, Molndal, Sweden
关键词
Epigenetics; Methylation; Diabetes; Pregnancy; Gestational diabetes; Fetal programming; GLUCOSE-METABOLISM; LEPTIN GENE; MATERNAL HYPERGLYCEMIA; INTRAUTERINE EXPOSURE; HUMAN PLACENTA; IN-UTERO; MELLITUS; OBESITY; RESISTIN; ADIPONECTIN;
D O I
10.1186/s13148-017-0338-2
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Offspring of women with diabetes in pregnancy are at increased risk of type 2 diabetes mellitus (T2DM), potentially mediated by epigenetic mechanisms. The adipokines leptin, adiponectin, and resistin (genes: LEP, ADIPOQ, RETN) play key roles in the pathophysiology of T2DM. We hypothesized that offspring exposed to maternal diabetes exhibit alterations in epigenetic regulation of subcutaneous adipose tissue (SAT) adipokine transcription. We studied adipokine plasma levels, SAT gene expression, and DNA methylation of LEP, ADIPOQ, and RETN in adult offspring of women with gestational diabetes (O-GDM, N = 82) or type 1 diabetes (O-T1DM, N = 67) in pregnancy, compared to offspring of women from the background population (O-BP, N = 57). Results: Compared to O-BP, we found elevated plasma leptin and resistin levels in O-T1DM, decreased gene expression of all adipokines in O-GDM, decreased RETN expression in O-T1DM, and increased LEP and ADIPOQ methylation in O-GDM. In multivariate regression analysis, O-GDM remained associated with increased ADIPOQ methylation and decreased ADIPOQ and RETN gene expression and O-T1DM remained associated with decreased RETN expression after adjustment for potential confounders and mediators. Conclusions: In conclusion, offspring of women with diabetes in pregnancy exhibit increased ADIPOQ DNA methylation and decreased ADIPOQ and RETN gene expression in SAT. However, altered methylation and expression levels were not reflected in plasma protein levels, and the functional implications of these findings remain uncertain.
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页数:12
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共 43 条
[1]   Mendelian randomization supports causality between maternal hyperglycemia and epigenetic regulation of leptin gene in newborns [J].
Allard, C. ;
Desgagne, V. ;
Patenaude, J. ;
Lacroix, M. ;
Guillemette, L. ;
Battista, M. C. ;
Doyon, M. ;
Menard, J. ;
Ardilouze, J. L. ;
Perron, P. ;
Bouchard, L. ;
Hivert, M. F. .
EPIGENETICS, 2015, 10 (04) :342-351
[2]  
[Anonymous], 2006, DEFINITION DIAGNOSIS
[3]   Modulation of adipokines and cytokines in gestational diabetes and macrosomia [J].
Ategbo, J. -M. ;
Grissa, O. ;
Yessoufou, A. ;
Hichami, A. ;
Dramane, K. L. ;
Moutairou, K. ;
Miled, A. ;
Grissa, A. ;
Jerbi, M. ;
Tabka, Z. ;
Khan, N. A. .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2006, 91 (10) :4137-4143
[4]   Early determinants of type-2 diabetes [J].
Berends, L. M. ;
Ozanne, S. E. .
BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM, 2012, 26 (05) :569-580
[5]   From leptin to other adipokines in health and disease: Facts and expectations at the beginning of the 21st century [J].
Blueher, Matthias ;
Mantzoros, Christos S. .
METABOLISM-CLINICAL AND EXPERIMENTAL, 2015, 64 (01) :131-145
[6]   Placental Adiponectin Gene DNA Methylation Levels Are Associated With Mothers' Blood Glucose Concentration [J].
Bouchard, Luigi ;
Hivert, Marie-France ;
Guay, Simon-Pierre ;
St-Pierre, Julie ;
Perron, Patrice ;
Brisson, Diane .
DIABETES, 2012, 61 (05) :1272-1280
[7]   Leptin Gene Epigenetic Adaptation to Impaired Glucose Metabolism During Pregnancy [J].
Bouchard, Luigi ;
Thibault, Stephanie ;
Guay, Simon-Pierre ;
Santure, Marta ;
Monpetit, Alexandre ;
St-Pierre, Julie ;
Perron, Patrice ;
Brisson, Diane .
DIABETES CARE, 2010, 33 (11) :2436-2441
[8]   Adipocytokines in obesity and metabolic disease [J].
Cao, Haiming .
JOURNAL OF ENDOCRINOLOGY, 2014, 220 (02) :T47-T59
[9]   High Prevalence of Type 2 Diabetes and Pre-Diabetes in Adult Offspring of Women With Gestational Diabetes Mellitus or Type 1 Diabetes The role of intrauterine hyperglycemia [J].
Clausen, Tine D. ;
Mathiesen, Elisabeth R. ;
Hansen, Torben ;
Pedersen, Oluf ;
Jensen, Dorte M. ;
Lauenborg, Jeannet ;
Damm, Peter .
DIABETES CARE, 2008, 31 (02) :340-346
[10]   Overweight and the Metabolic Syndrome in Adult Offspring of Women with Diet-Treated Gestational Diabetes Mellitus or Type 1 Diabetes [J].
Clausen, Tine D. ;
Mathiesen, Elisabeth R. ;
Hansen, Torben ;
Pedersen, Oluf ;
Jensen, Dorte M. ;
Lauenborg, Jeannet ;
Schmidt, Lone ;
Damm, Peter .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2009, 94 (07) :2464-2470