Maternal serum level of resistin is associated with risk for gestational diabetes mellitus: A meta-analysis

et al. 2020

Mol Med

Background: 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 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. Methods: Fetal 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. Results: Concentrations 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. Conclusions: Resistin 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.

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Fetal circulating human resistin increases in diabetes during pregnancy and impairs placental mitochondrial biogenesis

et al. 2020

Mol Med

“…A recent meta-analysis of 18 published studies (17) notes that resistin levels are elevated in maternal circulation in gestational diabetes. Much less is known about the determinants of resistin abundance in the fetal circulation and current reports regarding the association between cord blood resistin with diabetes during pregnancy are discordant (20)(21)(22).…”

Section: Discussionmentioning

confidence: 99%

“…Recent meta-analysis suggests GDM is associated with increased maternal resistin levels (17), while resutls of another meta-analysis do not indicate a signi cant change of resitin levels in gestational diabetes (18). Available prospective data are also inconsistent regarding the link of maternal resistin to the later development of GDM (19).…”

mentioning

confidence: 99%

Fetal circulating human resistin increases in diabetes during pregnancy and impairs placental mitochondrial biogenesis

et al. 2020

Preprint

Background: 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 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. Methods: Fetal 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.Results: Concentrations 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. Conclusions: Resistin 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.

“…Resistin has been implicated in the insulin resistance observed in normal pregnancy as the level of resistin increases with gestational age and decreases after delivery (17). The most recent meta-analysis suggests maternal resistin levels are associated with risk of GDM (18). However, current studies examining the fetal levels of resistin in diabetes during pregnancy are inconsistent (19)(20)(21).…”

Section: Discussionmentioning

confidence: 99%

Fetal circulating human resistin increases in diabetes during pregnancy and impairs placental mitochondrial biogenesis

et al. 2020

Preprint

Background Diabetes during pregnancy affects placental mitochondrial content and function, which can 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. Unlike rodents, human resistin is primarily secreted by monocytes or macrophages. The regulation and roles of human resistin in diabetes during pregnancy remain unclear. Methods Human resistin levels were measured in cord blood of women with diabetes during pregnancy (n=42) and healthy controls (n=81). Secretion of resistin from cord blood mononuclear cells (CBMCs) were measured. The actions of human resistin in mitochondrial biogenesis were determined on placental trophoblastic cells (BeWo cells) or human placental explant. Results Concentrations 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). 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. Conclusions In summary, we have shown that resistin is increased in fetal circulation of infants exposed to the diabetic milieu potentially reflecting the 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 .