Elevated fetal adipsin/acylation-stimulating protein (ASP) in obese pregnancy: novel placental secretion via Hofbauer cells

Abstract

Context and objective: Obesity in pregnancy is associated with increased risks of obesity in the offspring. We investigated the relationship between obesity in pregnancy and circulating maternal and fetal levels of adipose tissue-derived factors adipsin and acylation stimulating protein (ASP) in lean and obese mothers.

Design: Paired peripheral and cord blood samples were taken. Paired fat and placenta tissue were taken for explant culture. Media were assayed for secreted adipsin and ASP. Clinical parameters assayed included fasting insulin, glucose, and adipsin.

Setting: The study was conducted at a university hospital maternity unit.

Patients: Patients included 35 lean [body mass index (BMI) 19-25 kg/m(2), mean age 32 years and 39 obese (BMI) > 30 kg/m(2), mean age 32.49 years] pregnant Caucasian women, delivered by cesarean section at term.

Main outcome measure: Identification of placental macrophages [Hofbauer cells (HBCs)], as a source of adipsin and ASP was determined.

Results: HBCs secreted both adipsin and ASP. Cord levels of adipsin (1663.78 ± 52.76 pg/mL) and ASP (354.48 ± 17.17 ng/mL) were significantly elevated in the offspring of obese mothers compared with their lean controls [1354.66 ± 33.87 pg/mL and 302.63 ± 14.98 ng/mL, respectively (P < .05 for both)]. Placentae from obese mothers released significantly more adipsin and ASP than placentae from lean mothers [546.0 ± 44 pg/mL · g vs 284.56 ± 43 pg/mL · g and 5485.75 ± 163.32 ng/mL · g vs 2399.16 ± 181.83 ng/mL · g, respectively (P < .05 for both)]. Circulating fetal adipsin and ASP positively correlated with maternal BMI (r = 0.611, P < .0001, and r = 0.391, P < .05, respectively). Fetal adipsin correlated positively with maternal (r = 0.482, P < .01) and fetal homeostasis model assessment of insulin resistance (r = 0.465, P < .01).

Conclusions: We demonstrate novel secretion of adipsin and ASP by placental HBCs.

Figure 1.

Measurements of adipsin, ASP, and NEFA concentrations. A, Adipsin concentration in maternal and cord plasma. B, ASP concentration in maternal and cord plasma. C, Measurement of secreted adipsin from paired placental (n = 5) and adipose tissue explants (n = 5) between normal and obese patients. D, Measurement of secreted ASP from paired placental (n = 5) and adipose tissues explants (n = 5) between normal and obese patients. E, NEFA concentration in maternal and cord plasma. Cont, control. *, P < .05

Figure 2.

A, Relationship between fetal adipsin concentrations and maternal body mass index. B, Relationship between fetal ASP concentrations and maternal body mass index. C, Pearson correlation coefficients between fetal adipsin and fetal ASP with other covariates. P values are in brackets. NS, not significant; TG, triglycerides.

Figure 3.

Immunohistochemistry, immunofluorescence, and Western blotting. A, Immunohistochemical detection of adipsin in placental tissues; image was taken at ×10. B, Perivascular localization image taken at ×20. C, Western blotting of adipsin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in adipose (Ad.Tissue) and placental tissues. D, Immunofluorescence images of adipsin and CD206 revealing colocalization (upper panels) and adipsin and CK7 revealing no colocalization (lower panels).

Figure 4.

Measurement of adipsin (A) and ASP (B) secretions from isolated CTBs, FIBs, and HBCs. Significant secretion of adipsin and ASP was noted from HBCs. *, P < .001. HBC staining with CD206 in normal (C) and obese (D) placentae reveals increased numbers after counting using ImageJ (E). Macrophage staining with CD68 in normal (F) and obese (G) paired adipose tissue reveals increased numbers (H) after counting. Cont, control.