In:
Frontiers in Endocrinology, Frontiers Media SA, Vol. 12 ( 2021-12-24)
Abstract:
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 & 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 LEP 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 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.
Type of Medium:
Online Resource
ISSN:
1664-2392
DOI:
10.3389/fendo.2021.809916
DOI:
10.3389/fendo.2021.809916.s001
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2021
detail.hit.zdb_id:
2592084-4
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