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Multicenter Study
. 2021 Dec 24:12:809916.
doi: 10.3389/fendo.2021.809916. eCollection 2021.

Maternal Glucose and LDL-Cholesterol Levels Are Related to Placental Leptin Gene Methylation, and, Together With Nutritional Factors, Largely Explain a Higher Methylation Level Among Ethnic South Asians

Line Sletner  1   2 , Aina E F Moen  2   3   4 , Chittaranjan S Yajnik  5 , Nadezhda Lekanova  3 , Christine Sommer  6 , Kåre I Birkeland  7 , Anne K Jenum  8 , Yvonne Böttcher  2   3
Affiliations
Multicenter Study

Maternal Glucose and LDL-Cholesterol Levels Are Related to Placental Leptin Gene Methylation, and, Together With Nutritional Factors, Largely Explain a Higher Methylation Level Among Ethnic South Asians

Line Sletner et al. Front Endocrinol (Lausanne). .

Abstract

Background: Leptin, mainly secreted by fat cells, plays a core role in the regulation of appetite and body weight, and has been proposed as a mediator of metabolic programming. During pregnancy leptin is also secreted by the placenta, as well as being a key regulatory cytokine for the development, homeostatic regulation and nutrient transport within the placenta. South Asians have a high burden of type 2 diabetes, partly attributed to a "thin-fat-phenotype".

Objective: Our aim was to investigate how maternal ethnicity, adiposity and glucose- and lipid/cholesterol levels in pregnancy are related to placental leptin gene (LEP) DNA methylation.

Methods: We performed DNA methylation analyses of 13 placental LEP CpG sites in 40 ethnic Europeans and 40 ethnic South Asians participating in the STORK-Groruddalen cohort.

Results: South Asian ethnicity and gestational diabetes (GDM) were associated with higher placental LEP methylation. The largest ethnic difference was found for CpG11 [5.8% (95% CI: 2.4, 9.2), p<0.001], and the strongest associations with GDM was seen for CpG5 [5.2% (1.4, 9.0), p=0.008]. Higher maternal LDL-cholesterol was associated with lower placental LEP methylation, in particular for CpG11 [-3.6% (-5.5, -1.4) per one mmol/L increase in LDL, p<0.001]. After adjustments, including for nutritional factors involved in the one-carbon-metabolism cycle (vitamin D, B12 and folate levels), ethnic differences in placental LEP methylation were strongly attenuated, while associations with glucose and LDL-cholesterol persisted.

Conclusions: Maternal glucose and lipid metabolism is related to placental LEP methylation, whilst metabolic and nutritional factors largely explain a higher methylation level among ethnic South Asians.

Keywords: Leptin; cholesterol; ethnicity; gestational diabetes; methylation; placenta.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Mean placental LEP methylation (95% CI) in ethnic European and South Asian women.
See this image and copyright information in PMC

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References

    1. Lager S, Powell TL. Regulation of Nutrient Transport Across the Placenta. J Pregnancy (2012) 2012:179827. doi: 10.1155/2012/179827 - DOI - PMC - PubMed
    1. Butte NF. Carbohydrate and Lipid Metabolism in Pregnancy: Normal Compared With Gestational Diabetes Mellitus. Am J Clin Nutr (2000) 71(5):1256s–61s. doi: 10.1093/ajcn/71.5.1256s - DOI - PubMed
    1. Malassine A, Alsat E, Besse C, Rebourcet R, Cedard L. Acetylated Low Density Lipoprotein Endocytosis by Human Syncytiotrophoblast in Culture. Placenta (1990) 11(2):191–204. doi: 10.1016/S0143-4004(05)80180-8 - DOI - PubMed
    1. Friedman JM. Leptin and the Endocrine Control of Energy Balance. Nat Metab (2019) 1(8):754–64. doi: 10.1038/s42255-019-0095-y - DOI - PubMed
    1. Tessier DR, Ferraro ZM, Gruslin A. Role of Leptin in Pregnancy: Consequences of Maternal Obesity. Placenta (2013) 34(3):205–11. doi: 10.1016/j.placenta.2012.11.035 - DOI - PubMed

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