DNA methylation of leptin and adiponectin promoters in children is reduced by the combined presence of obesity and insulin resistance

García-Cardona, M C; Huang, Fengyang; Garcia-Vivas, Jessica M.; López-Camarillo, César; Navarro, Blanca E. del Río; Navarro-Olivos, Efraín; Hong-Chong, E.; Bolaños-Jiménez, Francisco; Marchat, Laurence A.

doi:10.1038/ijo.2014.30

Cited by 92 publications

(78 citation statements)

References 37 publications

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“…It was reported that gestational high-fat diet decreases promoter methylation of leptin in the offspring (Khalyfa et al 2013). In humans, the concentration of circulating leptin is altered by obesity and the promoter methylation of leptin is also altered in obese individuals (Garcia-Cardona et al 2014). Moreover, previous published results suggest that the maternal metabolic status before and during pregnancy can alter placental LEP DNA methylation profile at birth and might contribute to metabolic programming of obesity and related conditions (Lesseur et al 2014b).…”

Section: Epigenetic Regulation Of Leptin and Its Consequences On Fetamentioning

confidence: 96%

Involvement of leptin in the molecular physiology of the placenta

Schanton¹,

Maymó²,

Pérez-Pérez³

et al. 2018

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Leptin is a homeostatic regulator in the placenta where it promotes proliferation, protein synthesis and the expression of tolerogenic maternal response molecules such as HLA-G. Leptin also exerts an anti-apoptotic action in placenta controlling the expression of p53 master cell cycle regulator under different stress conditions. On the other hand, leptin is an integrative target of different placental stimuli

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Section: Epigenetic Regulation Of Leptin and Its Consequences On Fetamentioning

confidence: 96%

Involvement of leptin in the molecular physiology of the placenta

Schanton¹,

Maymó²,

Pérez-Pérez³

et al. 2018

Reproduction

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“…In the adipose tissue of diet induced obese (DIO) mice, the methylated fraction of the leptin promoter was decreased by feeding a high-fat diet at the initial stage; however, it increased after 12 weeks of feeding a high-fat diet compared to control and low-fat diet mice [77]. In peripheral blood samples from human obese adolescents, methylation of the LEP promoter was shown to be negatively associated with BMI [78]. Moreover, obese patients who responded to a low-calorie-diet treatment with a weight loss higher than 5% exhibited lower leptin methylation levels in subcutaneous adipose tissue than those who lost less than 5% of their initial body weight [79].…”

Section: Epigenetic Regulation Of Leptin-related Signalling Pathways:mentioning

confidence: 96%

Leptin resistance in obesity: An epigenetic landscape

et al. 2015

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“…S2 -Garc ıa-Cardona) in leucocytes were associated with higher BMI and higher insulin resistance in adolescents. 39 However, whether the epigenetic modulation of LEP genomic region induced by exposure to maternal hyperglycemia is truly maintained later in life will need to be tested in longitudinal studies. The putative long-term effect of LEP epigenetic modulation on child health could be due to programming of adipocytes (i.e., maintaining a relatively lower DNAm levels throughout life) or to modulation of circulating perinatal leptin levels at a critical period of hypothalamic development.…”

Section: Discussionmentioning

confidence: 99%

Mendelian randomization supports causality between maternal hyperglycemia and epigenetic regulation of leptin gene in newborns

et al. 2015

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Leptin is an adipokine that acts in the central nervous system and regulates energy balance. Animal models and human observational studies have suggested that leptin surge in the perinatal period has a critical role in programming long-term risk of obesity. In utero exposure to maternal hyperglycemia has been associated with increased risk of obesity later in life. Epigenetic mechanisms are suspected to be involved in fetal programming of long term metabolic diseases. We investigated whether DNA methylation levels near LEP locus mediate the relation between maternal glycemia and neonatal leptin levels using the 2-step epigenetic Mendelian randomization approach. We used data and samples from up to 485 mother-child dyads from Gen3G, a large prospective population-based cohort. First, we built a genetic risk score to capture maternal glycemia based on 10 known glycemic genetic variants (GRS 10 ) and showed it was an adequate instrumental variable (b D 0.046 mmol/L of maternal fasting glucose per additional risk allele; SE D 0.007; P D 7.8 £ 10 ¡11 ; N D 467). A higher GRS 10 was associated with lower methylation levels at cg12083122 located near LEP (b D ¡0.072 unit per additional risk allele; SE D 0.04; P D 0.05; N D 166). Direction and effect size of association between the instrumental variable GRS 10 and methylation at cg12083122 were consistent with the negative association we observed using measured maternal glycemia. Lower DNA methylation levels at cg12083122 were associated with higher cord blood leptin levels (b D ¡0.17 log of cord blood leptin per unit; SE D 0.07; P D 0.01; N D 170). Our study supports that maternal glycemia is part of causal pathways influencing offspring leptin epigenetic regulation.

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DNA methylation of leptin and adiponectin promoters in children is reduced by the combined presence of obesity and insulin resistance

Cited by 92 publications

References 37 publications

Involvement of leptin in the molecular physiology of the placenta

Involvement of leptin in the molecular physiology of the placenta

Leptin resistance in obesity: An epigenetic landscape

Mendelian randomization supports causality between maternal hyperglycemia and epigenetic regulation of leptin gene in newborns

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