A5064562324- Birth, Development, and Health
- Adipose Tissue and Metabolism
- Regulation of Appetite and Obesity
- Sodium Intake and Health
- Signaling Pathways in Disease
- Liver Disease Diagnosis and Treatment
- Stress Responses and Cortisol
- Hormonal Regulation and Hypertension
- Cardiac Fibrosis and Remodeling
- Adipokines, Inflammation, and Metabolic Diseases
- Cardiomyopathy and Myosin Studies
- Cardiac Ischemia and Reperfusion
- Diabetes and associated disorders
- Lymphatic System and Diseases
- Nitric Oxide and Endothelin Effects
- Cardiac Arrhythmias and Treatments
- Photosynthetic Processes and Mechanisms
- Thermoregulation and physiological responses
- Reproductive System and Pregnancy
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Electrolyte and hormonal disorders
- Gestational Diabetes Research and Management
- Molecular spectroscopy and chirality
- Burn Injury Management and Outcomes
- Cardiac Arrest and Resuscitation
Cardiovascular Institute of the South
2006-2024
Stanford University
2023-2024
Haukeland University Hospital
2022-2023
University of Bergen
2018-2023
Palo Alto University
2023
King's College London
2007-2018
St Thomas' Hospital
2013-2017
Kings Health Partners
2013-2014
University of Cambridge
2007
National Institute for Public Health and the Environment
2007
Maternal obesity is increasingly prevalent and may affect the long-term health of child. We investigated effects maternal diet-induced in mice on offspring metabolic cardiovascular function. Female C57BL/6J were fed either a standard chow (3% fat, 7% sugar) or palatable obesogenic diet (16% 33% for 6 weeks before mating throughout pregnancy lactation. Offspring control (OC) obese dams (OO) weaned onto studied at 3 months age. OO hyperphagic from 4 to age compared with OC locomotor activity...
Hypothalamic systems which regulate appetite may be permanently modified during early development. We have previously reported hyperphagia and increased adiposity in the adult offspring of rodents fed an obesogenic diet prior to throughout pregnancy lactation. now report that obese (OffOb) rats display amplified prolonged neonatal leptin surge, is accompanied by elevated mRNA expression their abdominal white adipose tissue. At postnatal Day 30, before onset these animals, serum normal, but...
During pregnancy, infection or immune responses induce cytokine release, which might influence fetal neurodevelopment, leading to neurodegenerative disease in adulthood. Because the hippocampus is a key area for learning and memory, we evaluated 4- 24-wk-old rats effects of early late prenatal exposure interleukin-6 (IL-6) on hippocampal morphology, expression mRNA IL-6, gamma-aminobutyric acid receptor (GABA(Aalpha5)), NR1 subunit N-methyl-D-aspartate receptor, glial fibrillary acidic...
Abstract The global prevalence of obesity-induced liver disease (nonalcoholic fatty disease; NAFLD) is rising. Suggested causes include a role for in utero influences maternal obesity compounded by the availability energy-dense foods throughout postnatal life. Using physiologically relevant model, we investigated innate immune system injury induced followed obesogenic diet. Female C57BL/6J mice were fed standard or diet before and pregnancy during lactation. offspring weaned onto at 3 weeks...
Maternal obesity in rodents is associated with increased adiposity, impaired glucose tolerance, and hypertension adult offspring. In this study we investigated the influence of maternal rat on blood pressure regulatory pathways juvenile Obesity was induced before pregnancy female Sprague-Dawley rats by feeding a highly palatable energy-dense diet. animals (30 days age), onset hyperleptinemia, basal nighttime mean arterial significantly raised offspring obese dams (OffOb) relative to controls...
To investigate the association between hyperinsulinemia and cardiac hypertrophy, we treated rats with insulin for 7 wk assessed effects on myocardial growth, vascularization, fibrosis in relation to expression of angiotensin II receptors (AT-R). We also characterized signaling pathways believed promote myocyte growth interact proliferative responses mediated by G protein-coupled receptors, receptor substrate-1 (IRS-1) p110 alpha catalytic p85 regulatory subunits phospatidylinositol 3 kinase...
Eating an unbalanced diet during pregnancy may induce long-term health consequences in offspring, particular obesity, insulin resistance and hypertension. We tested the hypothesis that a maternal rich simple sugars predispose mouse offspring to glucose intolerance cardiovascular diseases adulthood. Female C57BL/6J mice were fed either standard chow or sucrose-rich (26% of total energy) 6 weeks prior mating, throughout lactation. Offspring control dams (OC) high sucrose (OSF) weaned onto...
During pregnancy, systemic inflammatory responses induce cytokines that may stress the fetus and contribute to cardiovascular neuroendocrine dysfunction in adulthood. We evaluated effects of early late prenatal exposure IL-6 on mean systolic arterial pressure (MSAP) hypothalamic-pituitary-adrenal (HPA) axis regulation male female rats at 5-24 wk age. MSAP ACTH corticosterone levels were measured basally response a novel environment, immobilization stress, stimulation with...
Cross-fostering is widely used in developmental programming studies to determine the relative contribution of utero and suckling periods establishing adult offspring phenotype response an environmental challenge. We have investigated whether process fostering per se influences cardiovascular metabolic function C57BL/6J mice comparison with animals suckled by their biological dams. Cross-fostered (CF) demonstrated juvenile onset hyperphagia significantly higher body weight (from weaning 12...
Background: Recent studies have indicated that sodium storage is influenced by macrophages secrete VEGF-C (vascular endothelial growth factor) during salt stress thus stimulating lymphangiogenesis, thereby acting as a buffer against increased blood pressure (BP). We aimed to explore the role of dermal lymphatics in BP and homeostasis. Our hypothesis was mice with reduced lymphatic vessels were more prone develop salt-sensitive hypertension, hyperplastic protected. Methods: Mice either...
Cytokines are emerging as important in developmental processes. They may induce alterations normal gene expression patterns, activate angiotensinogen transcription, or alter of the renin-angiotensin system (RAS). To determine whether prenatal exposure to interleukin-6 (IL-6) influences intrarenal RAS and contributes renal dysfunction hypertension adulthood, we exposed female rats IL-6 early (EIL-6 females) late (LIL-6 pregnancy analysed blood pressure offspring at 5-20 weeks age. Renal fluid...
Inhalation injury is an important contributor to morbidity and mortality in burn victims can trigger acute lung respiratory distress syndrome (ARDS) (1–3). Early diagnosis treatment of inhalation are important, but a major problem planning evaluating the prognosis has been lack consensus about diagnostic criteria (4). Chest radiographs on admission often non-specific (5, 6), indicators include indoor fires, facial burns, bronchoscopic findings soot airways, detection carbon monoxide or...
Obesity is a heterogeneous phenotype and risk associations to non-communicable diseases such as cardiovascular disease type 2 diabetes are influenced by several factors. The paternal metabolic status at the time of conception influences offspring susceptibility developing obesity adiposity-associated cardiometabolic disease. Cholestatic liver characterized raised circulating serum bile acid levels dyslipidemia, commonly treated with ursodeoxycholic (UDCA). We hypothesized that cholestasis...
Material obesity in rodents is associated with neonatal hyperleptinemia and hypertension of sympathetic origin adult offspring. Previously, we reported that experimentally induced rat pups results adulthood hypertension. Here, addressed the hypothesis experimental hyperleptinemia, through renal nerve activation, adversely affects function.Sprague-Dawley male female were treated leptin (3 mg/kg, intraperitoneal) or saline, twice daily from postnatal day 9-14. Juvenile (1 month) saline rats...
Maternal obesity predisposes offspring to metabolic dysfunction and Non-Alcoholic Fatty Liver Disease (NAFLD). Melanocortin-4 receptor (Mc4r)-deficient mouse models exhibit during adulthood. Here, we aim determine the influence of Mc4r gene on liver mice subjected perinatal diet-induced obesity. Female heterozygous for fed an obesogenic or a control diet 5 weeks were mated with males, same continued throughout pregnancy lactation, generating four groups: wild type (C_wt), knockout (C_KO),...
In rats, a maternal diet rich in lard is associated with reduced Na(+),K(+)-ATPase activity adult offspring kidney. We have addressed the role of different fatty acids by evaluating dams fed diets saturated (SFA), monounsaturated (MUFA) or polyunsaturated (PUFA) acids. Female Sprague-Dawley rats were fed, during pregnancy and suckling, control (4% w/w corn oil) acid supplemented (24% w/w). Offspring reared on chow PUFA) studied at 6 months. mRNA expression (real-time PCR) alpha subunit...
Familial dilated cardiomyopathy is a prevalent cause of heart failure that results from the mutation genes encoding proteins diverse function. Despite modern therapy, typically has poor outcome and leading cardiac transplantation. The phosphatase PP2A at cardiomyocyte perinuclear mAKAPβ signalosomes promotes pathological eccentric remodeling, as characteristic cardiomyopathy. Displacement mAKAPβ, inhibiting function in intracellular compartment, can be achieved by expression mAKAPβ-derived...
Myocardial infarction (MI) is a major cause of mortality and morbidity worldwide. Heart failure due to MI results from both acute ischemia/reperfusion (I/R) injury subsequent post-MI pathological cardiac remodeling. The Ca 2+ /calmodulin-dependent protein phosphatase calcineurin (CaN) critical mediator Along with its role in the immune system, pro-survival function CaN complicates targeting heart disease. CaNAβ isoform uniquely associated hypertrophy. We have discovered that pools...
The β-adrenergic receptor is a prototypical G-protein coupled that initiates signaling from the plasma membrane. However, active receptors have been detected within intracellular compartments. functional significance of these remains unclear, including whether they regulate distinct cellular processes or function independently membrane receptors. We show using live cell imaging primary cardiomyocytes localized to Golgi apparatus opposing outer nuclear are sufficient and necessary for...
Abstract Aims Cardiac energy metabolism is centrally involved in heart failure (HF), although the direction of metabolic alterations complex and likely dependent on particular stage HF progression. Vascular endothelial growth factor B (VEGF-B) has been shown to modulate processes induce physiological cardiac hypertrophy; thus, it could be cardioprotective failing myocardium. This study investigates role VEGF-B proteomic adaptation during aldosterone high-salt hypertensive challenges. Methods...
Objective: Maternal obesity in rodents leads to sympathetic mediated hypertension the juvenile offspring prior obesity. This is associated with an exaggerated leptin surge early postnatal life. The aim of this study was determine impact neonatal on long-term renal structure and function, independent presence hypertension, using a normotensive melanocortin-4 receptor deficient (MC4R -/-) mice model. Design method: Neonatal were treated (L-Tx; 3 mg/kg IP) or saline (S-Tx), day 9–14. Mean...