Cerebrospinal fluid levels of insulin, leptin, and agouti‐related protein in relation to BMI in pregnant women

Abstract

Objective: During pregnancy, metabolic interactions must be adapted, though neuroendocrine mechanisms for increased food intake are poorly understood. The objective of this study was to characterize differences in insulin, leptin, and agouti-related protein (AgRP) levels in serum and cerebrospinal fluid (CSF) in pregnant women with normal weight (NW) and pregnant women with overweight (OW) or obesity (OB). Placenta as a source for increased peripheral AgRP levels during pregnancy was also investigated. Methods: Women were recruited at admission for elective cesarean section. Insulin, AgRP, and leptin were measured in serum and CSF from 30 NW, 25 OW, and 21 OB at term. Serum during pregnancy and placenta at term were collected for further AgRP analysis. Results: Immunohistology showed placental production of AgRP and serum AgRP levels increased throughout pregnancy. CSF AgRP, leptin, and insulin levels were higher in OW and OB than NW. Serum leptin and insulin levels were higher and AgRP lower in OB than NW. Conclusions: High serum AgRP levels might protect from the suppressive effects of leptin during pregnancy. Pregnant women with OB and OW might further be protected from the suppressive effect of leptin by high CSF AgRP levels. Evidence was found, for the first time, of human placental AgRP production mirrored by levels in the circulation.

Central and peripheral leptin and agouti‐related protein during and after pregnancy in relation to weight change

“…Due to availability of pregnancy samples, peripheral levels of AgRP was analysed in serum even though plasma is often used. Previous reports have analysed serum AgRP, and we have performed a validation where 32 serum and plasma samples from pregnant women assayed for AgRP in parallel gave good correlations ( R = .8, P < .001). Samples were analysed undiluted using ELISA (R&D systems, recombinant full‐length human AgRP standard).…”

“…Informed consent was obtained from all participants. All 74 women from our earlier study were contacted by phone, and 25 agreed to participate in this follow‐up study. The cohort is depicted in Figure .…”

“…The first 0.5 mL was discarded. Study samples were centrifuged, aliquoted and stored (−80°C) as described . Because of technical difficulties or unwillingness to undergo sampling, CSF was obtained from 17 of the 25 women.…”

“…As only one variable (AgRP) was significant, no multivariate analyses were done. For determination of Michaelis‐Menten type kinetics for saturable transport of leptin, all measurements from our previous pregnancy study were included (n = 58), and a nonlinear regression analysis was done with the following model: [Leptin] CSF = V max [Leptin] serum /([Leptin] serum + K m ). P < .05 was considered significant.…”

“…Previously, we found that placental production of AgRP and serum (s) AgRP levels increased throughout pregnancy but with great interindividual variation. Cerebrospinal fluid (CSF) AgRP, leptin and insulin concentrations were higher, and the s‐AgRP concentration was lower, in overweight and obese women than in those of normal weight . Thus, both central and peripheral AgRPs may interact with effects of leptin and insulin to meet the physiological and metabolic demands of pregnancy.…”