Abstract
BackgroundDiabetes during pregnancy affects placental mitochondrial content and function, which has the potential to impact fetal development and the long-term health of offspring. Resistin is a peptide hormone originally discovered in mice as an adipocyte-derived factor that induced insulin resistance. In humans, resistin is primarily secreted by monocytes or macrophages. The regulation and roles of human resistin in diabetes during pregnancy remain unclear.MethodsFetal resistin levels were measured in cord blood from pregnancies with (n = 42) and without maternal diabetes (n = 81). Secretion of resistin from cord blood mononuclear cells (CBMCs) was measured. The actions of human resistin in mitochondrial biogenesis were determined in placental trophoblastic cells (BeWo cells) or human placental explant.ResultsConcentrations of human resistin in cord sera were higher in diabetic pregnancies (67 ng/ml) compared to healthy controls (50 ng/ml, P < 0.05), and correlated (r = 0.4, P = 0.002) with a measure of maternal glycemia (glucose concentration 2 h post challenge). Resistin mRNA was most abundant in cord blood mononuclear cells (CBMCs) compared with placenta and mesenchymal stem cells (MSCs). Secretion of resistin from cultured CBMCs was increased in response to high glucose (25 mM). Exposing BeWo cells or human placental explant to resistin decreased expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), mitochondrial abundance, and ATP production.ConclusionsResistin is increased in fetal circulation of infants exposed to the diabetic milieu, potentially reflecting a response of monocytes/macrophages to hyperglycemia and metabolic stresses associated with diabetes during pregnancy. Increased exposure to resistin may contribute to mitochondrial dysfunction and aberrant energy metabolism characteristic of offspring exposed to diabetes in utero.
Highlights
Diabetes during pregnancy affects placental mitochondrial content and function, which has the potential to impact fetal development and the long-term health of offspring
Human resistin inhibits placental mitochondrial biogenesis We previously reported a decrease in the Peroxisome proliferatoractivated receptor gamma coactivator 1-alpha (PGC-1α)/ TFAM mitochondrial biogenesis pathway in placenta of mothers with diabetes (Jiang et al 2017)
The present study demonstrates that an increase in cord blood resistin found in the presence of maternal diabetes may play a role in placental mitochondrial biogenesis and function
Summary
Diabetes during pregnancy affects placental mitochondrial content and function, which has the potential to impact fetal development and the long-term health of offspring. Resistin is a secreted protein implicated in the pathogenesis of obesity and type 2 diabetes It was discovered in rodents as an adipocyte-derived factor which induces insulin resistance (Steppan et al 2001). Given the strong relationship between inflammation and metabolism, there is mounting evidence suggesting a role for human resistin in the pathological processes of metabolic diseases, including obesity, diabetes, and cardiovascular diseases (Lazar 2007; McTernan et al 2002). Recent meta-analysis suggests GDM is associated with increased maternal resistin levels (Hu et al 2019), while resutls of another meta-analysis do not indicate a significant change of resitin levels in gestational diabetes (Bellos et al 2019). The aims of the present study are to assess the regulation and function of human resistin in fetal circulation and how it affects placenta in diabetes during pregnancy
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