AUTHOR=Sletner Line , Moen Aina E. F. , Yajnik Chittaranjan S. , Lekanova Nadezhda , Sommer Christine , Birkeland Kåre I. , Jenum Anne K. , Böttcher Yvonne 

TITLE=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

JOURNAL=Frontiers in Endocrinology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2021.809916

DOI=10.3389/fendo.2021.809916

ISSN=1664-2392

ABSTRACT=<sec><title>Background</title><p>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”.</p></sec><sec><title>Objective</title><p>Our aim was to investigate how maternal ethnicity, adiposity and glucose- and lipid/cholesterol levels in pregnancy are related to placental leptin gene (<italic>LEP</italic>) DNA methylation.</p></sec><sec><title>Methods</title><p>We performed DNA methylation analyses of 13 placental <italic>LEP</italic> CpG sites in 40 ethnic Europeans and 40 ethnic South Asians participating in the STORK-Groruddalen cohort.</p></sec><sec><title>Results</title><p>South Asian ethnicity and gestational diabetes (GDM) were associated with higher placental <italic>LEP</italic> methylation. The largest ethnic difference was found for CpG11 [5.8% (95% CI: 2.4, 9.2), p&lt;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 <italic>LEP</italic> methylation, in particular for CpG11 [-3.6% (-5.5, -1.4) per one mmol/L increase in LDL, p&lt;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 <italic>LEP</italic> methylation were strongly attenuated, while associations with glucose and LDL-cholesterol persisted.</p></sec><sec><title>Conclusions</title><p>Maternal glucose and lipid metabolism is related to placental <italic>LEP</italic> methylation, whilst metabolic and nutritional factors largely explain a higher methylation level among ethnic South Asians.</p></sec>