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High Molecular Mass Multimer Complexes and Vascular Expression Contribute to High Adiponectin in the Fetus

Women and Infant Hospital Rhode Island (H.P., M.C.), Department Obstetrics and Gynecology, Brown University, Providence, Rhode Island 02912; and Case Western Reserve University (S.B., K.H., L.L., L.P., P.M.C., S.H.-d.M.), Department Reproductive Biology, MetroHealth Medical Center, Cleveland, Ohio 44109

Address all correspondence and requests for reprints to: S. Hauguel-de Mouzon, Case Western Reserve University, Department Reproductive Biology, MetroHealth Medical Center, 2500 MetroHealth Drive, Cleveland, Ohio 44109. E-mail: shdemouzon{at}metrohealth.org.

Context: High plasma adiponectin concentrations in human fetuses and neonates are unique features of early developmental stages. Yet, the origins of the high adiponectin concentrations in the perinatal period remain elusive.

Objective: This study was undertaken to identify the sources and functional properties of adiponectin in utero.

Design and Methods: Tissue specimens were obtained at autopsy from 21- to 39-wk-old stillborn human fetuses. Adipose tissue and placenta were obtained at term elective cesarean section. Adiponectin complexes and expression were measured by immunodetection and real-time PCR.

Results: Adiponectin mRNA transcripts were detected in fetal sc and omental adipose depots at lower concentrations than in maternal adipose tissue. Immunoreactive adiponectin was also observed in vascular endothelial cells of fetal organs, including skeletal muscle, kidney, and brain. The absence of adiponectin in all placental cell types and lack of correlation between maternal and umbilical adiponectin indicate that umbilical adiponectin reflects its exclusive production by fetal tissues. The most prominent forms of adiponectin in fetal plasma were high and low molecular mass (HMW and LMW) multimers of 340 and 160 kDa, respectively. The proportion of the HMW complexes was 5-fold (P < 0.001) higher in umbilical plasma than in adult. The high HMW and total adiponectin levels were associated with lower insulin concentration and lower homeostasis model of assessment of insulin resistance indices in umbilical plasma, reflecting higher insulin sensitivity of the fetus compared with adult.

Conclusions: The abundance of HMW adiponectin and its vascular expression are characteristics of human fetal adiponectin. Combined with high insulin sensitivity, fetal adiponectin may be a critical determinant of in utero growth.