A5062138185- Birth, Development, and Health
- Pregnancy and preeclampsia studies
- Gestational Diabetes Research and Management
- Adipose Tissue and Metabolism
- Pancreatic function and diabetes
- Metabolism and Genetic Disorders
- Diet and metabolism studies
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Regulation of Appetite and Obesity
- Liver Disease Diagnosis and Treatment
- Obesity, Physical Activity, Diet
- Neonatal Respiratory Health Research
- Diet, Metabolism, and Disease
- Diabetes and associated disorders
- Growth Hormone and Insulin-like Growth Factors
- Fatty Acid Research and Health
- Animal Nutrition and Physiology
- Metabolism, Diabetes, and Cancer
- Genetic Syndromes and Imprinting
- Epigenetics and DNA Methylation
- Mitochondrial Function and Pathology
- Muscle Physiology and Disorders
- Congenital Diaphragmatic Hernia Studies
- Single-cell and spatial transcriptomics
- Reproductive Physiology in Livestock
University of Colorado Denver
2016-2025
University of Colorado Anschutz Medical Campus
2015-2025
University of Colorado Health
2024
Children's Hospital Colorado
2020
University of Arizona
2016
Oregon Health & Science University
2016
University of Manchester
2016
University of Maryland, College Park
2016
Augusta University
2016
Michigan State University
2004
Intrauterine growth-restricted (IUGR) fetal sheep, produced by placental insufficiency, have lower oxygen concentrations, higher lactate and increased hepatic glucose production that is resistant to suppression insulin. We hypothesized in the IUGR fetus results from reduced oxidation, during basal maximal insulin-stimulated conditions, used support production. To test this, studies were performed late-gestation control (CON) sheep under hyperinsulinemic-clamp conditions. The oxidation rate...
Maternal overnutrition increases inflammatory and metabolic disease risk in postnatal offspring. This constitutes a major public health concern due to increasing prevalence of these diseases, yet mechanisms remain unclear. Here, using nonhuman primate models, we show that maternal Western-style diet (mWSD) exposure is associated with persistent pro-inflammatory phenotypes at the transcriptional, metabolic, functional levels bone marrow-derived macrophages (BMDMs) from 3-year-old juvenile...
Adults who were affected by intrauterine growth restriction (IUGR) suffer from reductions in muscle mass, which may contribute to insulin resistance and the development of diabetes. We demonstrate slower hindlimb linear protein synthesis rates that match reduced blood flow oxygen consumption IUGR fetal sheep. These adaptations resulted similar control fetuses on a weight-specific basis. Net glucose uptake lactate output between groups, whereas amino acid was significantly lower Among all...
ABSTRACT Background and Aims Maternal obesity increases the risk of paediatric form metabolic dysfunction‐associated steatotic liver disease (MASLD), affecting up to 30% youth, but developmental origins remain poorly understood. Methods Using a Japanese macaque model, we investigated impact maternal Western‐style diet (mWSD) or chow followed by postweaning WSD (pwWSD) focusing on bile acid (BA) homeostasis hepatic fibrosis in livers from third‐trimester fetuses 3‐year‐old juvenile offspring....
Postnatally, glucagon acutely lowers plasma amino acid (AA) concentrations by stimulating hepatic AA catabolism, but its fetal actions remain unclear. This study tested whether a 2 h infusion would stimulate catabolism and inhibit placental transfer. Late-gestation pregnant sheep (0.9 gestation) underwent surgical, vascular catheterization received (n = 8) or vehicle infusions in crossover design with 48 washout period. Nutrient uptake utilization were assessed during each infusion, liver...
Non-alcoholic fatty liver disease (NAFLD) risk begins in utero offspring of obese mothers. A critical unmet need this field is to understand the pathways and biomarkers underlying fetal hepatic lipotoxicity whether maternal dietary intervention during pregnancy an effective countermeasure. We utilized a well-established non-human primate model chronic, maternal, Western-style diet induced obesity (OB-WSD) compared with mothers on healthy control (CON) or subset OB-WSD switched CON (diet...
Placental insufficiency is associated with reduced supply of amino acids to the fetus and leads intrauterine growth restriction (IUGR). IUGR fetuses are characterized by lower glucose-stimulated insulin secretion, smaller pancreatic islets less β-cells, impaired vascularity. To test whether supplemental infused into could improve these complications we used acute (hours) chronic (11 d) direct fetal acid infusions a sheep model placental near end gestation. had attenuated acid-stimulated...
Adults who were affected by intrauterine growth restriction (IUGR) suffer from reductions in muscle mass and insulin resistance, suggesting may be restricted molecular events that occur during fetal development. To explore the basis of growth, we used a sheep model progressive placental insufficiency-induced IUGR to assess myoblast proliferation within intact skeletal vivo isolated myoblasts stimulated with vitro Gastrocnemius soleus weights reduced 25% fetuses compared those controls (CON)....
Fetal insulin secretion is inhibited by acute hypoxemia. The relationship between prolonged hypoxemia and secretion, however, less well defined. To test the hypothesis that fetal impairs studies were performed in sheep fetuses bled to anemic conditions for 9 ± 0 days (anemic, n = 19) compared with control ( 15). Arterial hematocrit oxygen content 34% 52% lower, respectively, vs. P < 0.0001). Plasma glucose concentrations 21% higher group 0.05). norepinephrine cortisol increased 70%...
Infants of obese mothers have an increased risk developing obesity, insulin resistance, and type 2 diabetes. The underlying mechanisms remain elusive, no effective interventions to limit the transmission metabolic disease from mother her infant are currently available. Obese pregnant women decreased circulating levels adiponectin, which is associated with placental nutrient transport fetal overgrowth. We reported that normalization adiponectin during late gestation reversed dysfunction...
Studying fetal hematopoiesis is challenging as transitions from the liver to bone marrow. Obtaining human samples not possible, and small animal models may provide sufficient biological material. Here, we present a protocol for isolating hematopoietic cells nonhuman primate bone. We describe steps using same fetus fluorescence lifetime imaging microscopy measure metabolism, assessing cellular function, flow cytometry immunophenotyping at single-cell level. For complete details on use...
Mammals meet the increased nutritional demands of lactation through a combination feed intake and collection adaptations known as adaptive metabolism (e.g., glucose sparing via insulin resistance, mobilization endogenous reserves, metabolic efficiency reduced thyroid hormones). In modern dairy cow, predominates over at onset develops concurrently with reduction in plasma leptin. To address role leptin early lactation, we asked which could be countered by constant 96-h intravenous infusion...
Intrauterine growth-restricted (IUGR) fetal sheep have increased hepatic glucose production (HGP) that is resistant to suppression during a hyperinsulinemic-isoglycemic clamp (insulin clamp). We hypothesized the IUGR liver would activation of metabolic and signaling pathways support HGP inhibition insulin-signaling pathways. To test this, we used transcriptomic profiling with samples from control (CON) fetuses receiving saline or an insulin clamp. The had upregulation genes associated...
In a sheep model of intrauterine growth restriction (IUGR) produced from placental insufficiency, late gestation fetuses had smaller skeletal muscle mass, myofiber area, and slower protein accretion rates compared with normally growing fetuses. We hypothesized that IUGR fetal develops adaptations divert amino acids (AAs) activate pathways conserve substrates for other organs. placed hindlimb arterial venous catheters into (n = 10) control (CON, n 8) included an external iliac artery flow...
Infants born to mothers with obesity have a greater risk for childhood and metabolic diseases; however, the underlying biological mechanisms remain poorly understood. We used Japanese macaque model investigate whether maternal combined Western-style diet (WSD) impairs offspring muscle insulin action. Adult females were fed control or WSD prior during pregnancy through lactation, subsequently weaned WSD. Muscle glucose uptake signaling measured ex vivo in fetal (n = 5–8/group) juvenile...
Key points Fetal glucagon concentrations are elevated in the setting of placental insufficiency, hypoxia and stress hormones. Chronically adult result profound decreases amino acid lean body mass. Experimental elevation fetal a late‐gestation pregnant sheep results lower concentrations, protein accretion weight, addition to decreased function. This study demonstrates negative effect on growth, also provides first example hormone that negatively regulates nutrient transport blood flow....
Pediatric NAFLD has distinct and variable pathology, yet causation remains unclear. We have shown that maternal Western-style diet (mWSD) compared with chow (CD) consumption in nonhuman primates produces hepatic injury steatosis fetal offspring. Here, we define the role of mWSD postweaning (pwWSD) exposures on molecular mechanisms linked to development a cohort 3-year-old juvenile offspring exposed CD or followed by after weaning. used histologic, transcriptomic, metabolomic analyses...
Metformin is used by women during pregnancy to manage diabetes and crosses the placenta, yet its effects on fetus are unclear. We show that liver a site of metformin action in fetal sheep macaques, given relatively abundant OCT1 transporter expression hepatic uptake following infusion into sheep. To determine action, we performed studies primary hepatocytes from sheep, juvenile macaques. increases AMP-activated protein kinase (AMPK) signaling, decreases mammalian target rapamycin (mTOR)...
Abstract Maternal obesity contributes to an increased risk of lifelong morbidity and mortality for both the mother her offspring. In order better understand molecular mechanisms underlying these risks, we previously established extensively characterized a primate model in Macaca fuscata (Japanese macaque). prior studies have demonstrated that high fat, caloric dense maternal diet structures offspring’s epigenome, metabolome, intestinal microbiome. During course this work consistently...
Insulin-like growth factor-1 (IGF-1) is an important fetal factor. However, the role of IGF-1 in increasing placental blood flow, nutrient transfer, and availability to support protein accretion not well understood. Catheterized fetuses from late gestation pregnant sheep received intravenous infusion LR3 (LR3 IGF-1; n = 8) or saline (SAL; for 1 wk. Sheep then underwent a metabolic study measure uterine umbilical uptake rates, kinetic rates. By end infusion, weights were statistically...