Fredrick J. Rosario
Anschutz Medical Campus
mTORC2Internal medicineEndocrinologyFetusChemistryAdiponectinPlacentaTrophoblastMechanistic target of rapamycinPregnancyInsulinSyncytiotrophoblastAmino acid transporterAmino acidBiochemistryMedicinePI3K/AKT/mTOR pathwayBiologyCell biologymTORC1
43Publications
19H-index
1,305Citations
Publications 47
Newest
#1Owen Vaughan (UCL: University College London)H-Index: 22
#2Katarzyna Maksym (UCL: University College London)H-Index: 2
Last. Fredrick J. Rosario (Anschutz Medical Campus)H-Index: 19
view all 12 authors...
Fetal growth restriction (FGR) is a complication of pregnancy that reduces birth weight, markedly increases infant mortality and morbidity and is associated with later-life cardiometabolic disease. No specific treatment is available for FGR. Placentas of human FGR infants have low abundance of sodium-coupled neutral amino acid transporter 2 (Slc38a2/SNAT2), which supplies the fetus with amino acids required for growth. We determined the mechanistic role of placental Slc38a2/SNAT2 deficiency in t...
Source
#1Owen Vaughan (Anschutz Medical Campus)H-Index: 22
#2Fredrick J. Rosario (Anschutz Medical Campus)H-Index: 19
Last. Thomas Jansson (Anschutz Medical Campus)H-Index: 61
view all 10 authors...
Obesity in pregnant women causes fetal cardiac dysfunction and increases offspring cardiovascular disease risk but its effect on myocardial metabolism is unknown. We hypothesised that maternal obesity alters fetal cardiac expression of metabolism-related genes and shifts offspring myocardial substrate preference from glucose towards lipids. Female mice were fed control or obesogenic diets before and during pregnancy. Fetal hearts were studied in late gestation (embryonic day, E18.5; term{approx}...
Source
#1Irving L.M.H. Aye (Anschutz Medical Campus)H-Index: 18
#2Fredrick J. Rosario (Anschutz Medical Campus)H-Index: 19
Last. Thomas Jansson (Anschutz Medical Campus)H-Index: 61
view all 7 authors...
CONTEXT Circulating adiponectin levels are decreased in pregnant women with obesity or gestational diabetes, and this is believed to contribute to the insulin resistance and increased risk of fetal overgrowth associated with these conditions. However, the molecular mechanisms regulating adiponectin secretion from maternal adipose tissues in pregnancy are poorly understood. OBJECTIVES We tested the hypothesis that obesity in pregnancy is associated with adipose tissue insulin resistance and incre...
Source
#1Fredrick J. Rosario (Anschutz Medical Campus)H-Index: 19
#2Anita Kramer (Anschutz Medical Campus)H-Index: 7
Last. Thomas Jansson (Anschutz Medical Campus)H-Index: 61
view all 0 authors...
Intrauterine growth restriction (IUGR) is associated with reduced placental amino acid transport (AAT). However, it remains to be established if changes in AAT contribute to restricted fetal growth. We hypothesized that reduced in vivo placental AAT precedes the development of IUGR in baboons with maternal nutrient restriction (MNR). Baboons were fed either a control (ad libitum) or MNR diet (70% of control diet) from gestational day (GD) 30. At GD 140, in vivo transplacental AA transport was me...
Source
#1Irving L.M.H. Aye (University of Cambridge)H-Index: 18
#2Fredrick J. RosarioH-Index: 19
Last. Thomas Jansson (Anschutz Medical Campus)H-Index: 61
view all 7 authors...
In pregnancy, adiponectin serves as an endocrine link between maternal adipose tissue, placental function and fetal growth, with low adiponectin promoting placental function and fetal growth. Circulating adiponectin levels are decreased in obese pregnant women and in gestational diabetes, which is believed to contribute to the insulin resistance and increased risk of fetal overgrowth associated with these conditions. However, the molecular mechanisms governing adiponectin secretion from maternal...
Source
#1Romina Higa (UBA: University of Buenos Aires)H-Index: 15
#2Fredrick J. Rosario (Anschutz Medical Campus)H-Index: 19
Last. Alicia Jawerbaum (UBA: University of Buenos Aires)H-Index: 24
view all 5 authors...
Mechanistic target of rapamycin (mTOR) is essential for embryo development by acting as a nutrient sensor to regulate cell growth, proliferation and metabolism. Folate is required for embryonic ribosomal protein S6, a downstream target of mTOR Complex1, markedly reduced embryonic folate incorporation (-84%, p<0.01) and induced embryo normal embryonic development and it was recently reported that mTOR functions as a folate sensor. In this work we tested the hypothesis that mTOR functions as a fol...
1 CitationsSource
#1Fredrick J. Rosario (Anschutz Medical Campus)H-Index: 19
#2Sammy Pardo (University of Texas Health Science Center at San Antonio)H-Index: 2
Last. Thomas Jansson (Anschutz Medical Campus)H-Index: 61
view all 8 authors...
The placental villus syncytiotrophoblast, the nutrient-transporting and hormone-producing epithelium of the human placenta, is a critical regulator of fetal development and maternal physiology. However, the identities of the proteins synthesized and secreted by primary human trophoblast (PHT) cells remain unknown. Stable Isotope Labeling with Amino Acids in Cell Culture followed by mass spectrometry analysis of the conditioned media was used to identify secreted proteins and obtain information a...
Source
#1Amy C. Kelly (Anschutz Medical Campus)H-Index: 22
#2Anita Kramer (CU: University of Colorado Boulder)H-Index: 7
Last. Thomas Jansson (CU: University of Colorado Boulder)H-Index: 61
view all 5 authors...
Changes in placental function, in particular down-regulation of placental O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) in response to maternal stress and increased placental secretion of serotonin into the fetal circulation following maternal infection, have been mechanistically linked to adverse neurodevelopment in mice. We hypothesized that mechanistic target of rapamycin (mTOR) signaling is a key regulator of trophoblast serotonin synthesis and OGT protein expression and that ser...
1 CitationsSource
#1Fredrick J. Rosario (Anschutz Medical Campus)H-Index: 19
#2Theresa L. Powell (Anschutz Medical Campus)H-Index: 66
Last. Thomas Jansson (Anschutz Medical Campus)H-Index: 61
view all 5 authors...
Mechanistic Target of Rapamycin Complex 1 (mTORC1) serves as positive regulator of placental nutrient transport and mitochondrial respiration. The role of mTORC1 signaling in modulating other placental functions is largely unexplored. We used gene array following silencing of raptor to identify genes regulated by mTORC1 in primary human trophoblast (PHT) cells. Seven hundred and thirty-nine genes were differentially expressed; 487 genes were down-regulated and 252 up-regulated. Bioinformatic ana...
4 CitationsSource
#1Rebecca H. Jessel (Anschutz Medical Campus)H-Index: 1
#2Fredrick J. Rosario (Anschutz Medical Campus)H-Index: 19
Last. Theresa L. Powell (Anschutz Medical Campus)H-Index: 66
view all 10 authors...
Abstract Obese women have a ~two-fold higher risk to deliver an infant with neural tube defects (NTDs) despite folate supplementation. Placental transfer of folate is mediated by folate receptor alpha (FR-α), proton coupled folate transporter (PCFT), and reduced folate carrier (RFC). Decreased placental transport may contribute to NTDs in obese women. Serum folate levels were measured and placental tissue was collected from 13 women with normal BMI (21.9±1.9) and 11 obese women (33.1±2.8) underg...
2 CitationsSource