OBJECTIVETo 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 METHODSPlacental 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.RESULTSWe 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).CONCLUSIONSIGT 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.

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1 This study was undertaken to further investigate the eects of a sucrose-enriched diet on vascular function and insulin sensitivity in rats. 2 Male Sprague-Dawley rats were randomized to receive a sucrose-or regular rat chow-diet for 4 weeks. A ®rst group of sucrose-and chow-fed rats was instrumented with pulsed Doppler¯ow probes and intravascular catheters to determine blood pressure, heart rate, regional blood¯ows and insulin sensitivity in conscious rats. Insulin sensitivity was assessed by the euglycemic hyperinsulinemic clamp technique. Glucose transport activity was examined in isolated muscles by using the glucose analogue [ 3 H]-2-deoxy-D-glucose. A second group of sucrose-and chow-fed rats was used to obtain information regarding nitric oxide synthase (NOS) isozymes protein expression in muscles, and determine endothelin content in vascular tissues isolated from both dietary groups. 3 Sucrose feeding was found to induce insulin resistance, but had no eect on resting blood pressure, heart rate, or regional haemodynamics. This insulin resistance was accompanied by alteration in the vascular responses to insulin. Insulin-mediated skeletal muscle vasodilation was impaired, whereas the mesenteric vasoconstrictor response was potentiated in sucrose-fed rats. A reduction in eNOS protein content in muscle and an increase in vascular endothelin peptide were noted in these animals. Moreover, a reduction in insulin-simulated glucose transport activity was also noted in muscles isolated from sucrose-fed rats. 4 Together these data suggest that a cluster of metabolic and haemodynamic abnormalities occur in response to the intake of simple sugars in rats.