Identification of early transcriptome signatures in placenta exposed to insulin and obesity.

Objective: The purpose of this study was to investigate the effects of insulin on human placental transcriptome and biological processes in first-trimester pregnancy.

Study Design: Maternal plasma and placenta villous tissue were obtained at the time of voluntary termination of pregnancy (7-12 weeks) from 17 lean (body mass index, 20.9±1.

Patterns of adiponectin expression in term pregnancy: impact of obesity.

Context: Adiponectin (adpN) production is down-regulated in several situations associated with insulin resistance. The hypoadiponectinemia, which develops in late pregnancy, suggests a role of adpN in pregnancy-induced insulin resistance.

Objective: In obese pregnancy there is a decreased systemic adpN, which results from down-regulation of gene expression in adipose tissue.

Increased death of adipose cells, a path to release cell-free DNA into systemic circulation of obese women.

Remodeling of adipose tissue is required to support the expansion of adipose mass. In obesity, an increased death of adipocytes contributes to the accelerated cellular turnover. We have shown that obesity in pregnancy is associated with metabolic and immune alterations in the adipose tissue.

Molecular inflammation and adipose tissue matrix remodeling precede physiological adaptations to pregnancy.

Changes in adipose tissue metabolism are central to adaptation of whole body energy homeostasis to pregnancy. To gain insight into the molecular mechanisms supporting tissue remodeling, we have characterized the longitudinal changes of the adipose transcriptome in human pregnancy. Healthy nonobese women recruited pregravid were followed in early (8-12 wk) and in late (36-38 wk) pregnancy.

Molecular phenotype of monocytes at the maternal-fetal interface.

Objective: The purpose of this study was to gain insight into the pathways that are associated with inflammation at the maternal-fetal interface. This study examined the molecular characteristics of monocytes that were derived from the maternal circulation and the placenta of obese women.

Study Design: Mononuclear cells were isolated from placenta, venous maternal, and umbilical cord blood at term delivery; activated monocytes were separated with CD14 immunoselection.

Pregravid obesity associates with increased maternal endotoxemia and metabolic inflammation.

Obese pregnant women develop severe insulin resistance and enhanced systemic and placental inflammation, suggesting associated modifications of endocrine and immune functions. Activation of innate immunity by endotoxins/lipopolysaccharides (LPS) has been proposed as a mechanism for enhancing metabolic alterations in disorders with insulin resistance. The aim of this study was to characterize the immune responses developed by the adipose tissue (AT) and their potential links to maternal endotoxemia in pregnancy with obesity.

Differential regulation of genes for fetoplacental lipid pathways in pregnancy with gestational and type 1 diabetes mellitus.

Objective: Changes in metabolic homeostasis in pregnant diabetic women are potential determinants of increased adiposity of the fetus. The aim of this study was to characterize diabetes mellitus-induced changes in genes for fetoplacental energy metabolism in relation to fetal adiposity.

Study Design: Placentas of women with type 1 diabetes mellitus, gestational diabetes mellitus (GDM), or no complications were analyzed by microarray profiling.

In utero gender dimorphism of adiponectin reflects insulin sensitivity and adiposity of the fetus.

Circulating adiponectin reflects the degree of energy homeostasis and insulin sensitivity of adult individuals. Low abundance of the high molecular weight (HMW) multimers, the most active forms mediating the insulin-sensitizing effects of adiponectin, is indicative of impaired metabolic status. The increase in fetal adiponectin HMW compared with adults is a distinctive features of human neonates.

Prolactin and insulin ultradian secretion and adipose tissue lipoprotein lipase expression in severely obese women after bariatric surgery.

Background: Hyperprolactinemia is associated with obesity. Furthermore, in human adipose tissue cultured in vitro, prolactin (PRL) inhibited lipoprotein lipase (LPL) activity via functional PRL receptors.

Objective: To study PRL and insulin ultradian rhythm and subcutaneous adipose tissue LPL mRNA and protein expressions in severely obese women before and after malabsorptive bariatric surgery.

Modulation of proteinase K-resistant prion protein in cells and infectious brain homogenate by redox iron: implications for prion replication and disease pathogenesis.

The principal infectious and pathogenic agent in all prion disorders is a beta-sheet-rich isoform of the cellular prion protein (PrP(C)) termed PrP-scrapie (PrP(Sc)). Once initiated, PrP(Sc) is self-replicating and toxic to neuronal cells, but the underlying mechanisms remain unclear. In this report, we demonstrate that PrP(C) binds iron and transforms to a PrP(Sc)-like form (*PrP(Sc)) when human neuroblastoma cells are exposed to an inorganic source of redox iron.

Cell-specific metabolism and pathogenesis of transmembrane prion protein.

The C-transmembrane form of prion protein ((Ctm)PrP) has been implicated in prion disease pathogenesis, but the factors underlying its biogenesis and cyotoxic potential remain unclear. Here we show that (Ctm)PrP interferes with cytokinesis in cell lines where it is transported to the plasma membrane. These cells fail to separate following cell division, assume a variety of shapes and sizes, and contain multiple nuclei, some of which are pyknotic.

Protease-resistant human prion protein and ferritin are cotransported across Caco-2 epithelial cells: implications for species barrier in prion uptake from the intestine.

Foodborne transmission of bovine spongiform encephalopathy (BSE) to humans as variant Creutzfeldt-Jakob disease (CJD) has affected over 100 individuals, and probably millions of others have been exposed to BSE-contaminated food substances. Despite these obvious public health concerns, surprisingly little is known about the mechanism by which PrP-scrapie (PrP(Sc)), the most reliable surrogate marker of infection in BSE-contaminated food, crosses the human intestinal epithelial cell barrier. Here we show that digestive enzyme (DE) treatment of sporadic CJD brain homogenate generates a C-terminal fragment similar to the proteinase K-resistant PrP(Sc) core of 27-30 kDa implicated in prion disease transmission and pathogenesis.