A5020787812- Cardiovascular Disease and Adiposity
- Adipokines, Inflammation, and Metabolic Diseases
- Adipose Tissue and Metabolism
- Cardiovascular Health and Disease Prevention
- Bariatric Surgery and Outcomes
- Atherosclerosis and Cardiovascular Diseases
- Angiogenesis and VEGF in Cancer
- Nitric Oxide and Endothelin Effects
- Autophagy in Disease and Therapy
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Body Contouring and Surgery
- Molecular Biology Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
- Cardiac Valve Diseases and Treatments
- Diabetes Treatment and Management
- Lymphatic System and Diseases
- Wnt/β-catenin signaling in development and cancer
- Pancreatic function and diabetes
- Lipid metabolism and biosynthesis
- Venous Thromboembolism Diagnosis and Management
- Lipid metabolism and disorders
- Advanced Glycation End Products research
- Tissue Engineering and Regenerative Medicine
- Cardiovascular Health and Risk Factors
- Thermoregulation and physiological responses
Boston University
2014-2024
University School
2022
University of Bristol
2014
NIHR Bristol Cardiovascular Biomedical Research Unit
2014
Medical College of Wisconsin
2011
We previously reported that adenosine monophosphate-activated protein kinase (AMPK) activity is lower in adipose tissue of morbidly obese individuals who are insulin resistant than comparably people sensitive. However, the number patients and parameters studied were small. Here, we compared abdominal subcutaneous, epiploic, omental fat from 16 classified as sensitive or based on homeostatic model assessment resistance. confirmed AMPK diminished group. A custom PCR array revealed increases...
Abnormal endothelial function promotes atherosclerotic vascular disease in diabetes. Experimental studies indicate that disruption of insulin signaling, through the activity protein kinase C-β (PKCβ) and nuclear factor κB, reduces nitric oxide availability. We sought to establish whether similar mechanisms operate endothelium human diabetes mellitus.We measured expression response freshly isolated cells from patients with type 2 mellitus (n=40) nondiabetic controls (n=36). Unexpectedly, we...
Adipose tissue dysfunction plays a pivotal role in the development of insulin resistance obese individuals. Cell culture studies and gain-of-function mouse models suggest that canonical Wnt proteins modulate adipose expansion. However, no genetic evidence supports for endogenous dysfunction, noncanonical signaling remains largely unexplored. Here we provide from human, mouse, cell showing Wnt5a-mediated, contributes to obesity-associated metabolic by increasing inflammation. Wnt5a expression...
Endothelial dysfunction is linked to insulin resistance, inflammatory activation, and increased cardiovascular risk in diabetes mellitus; however, the mechanisms remain incompletely understood. Recent studies have identified proinflammatory signaling of wingless-type family member (Wnt) 5a through c-jun N-terminal kinase (JNK) as a regulator metabolic with potential relevance vascular function. We sought gain evidence that activation Wnt5a-JNK contributes impaired endothelial function...
Background High fat diet and its induced changes in glucose homeostasis, inflammation obesity continue to be an epidemic developed countries. The A2b adenosine receptor (A2bAR) is known regulate inflammation. We used a diet-induced murine knockout model investigate the role of this mediating metabolic correlated our findings obese patient samples. Methodology/Principal Findings Administration high fat, cholesterol (HFD) for sixteen weeks vastly upregulated expression A2bAR control mice,...
A low-grade state of adipose tissue inflammation associated with obesity has been linked to mechanisms systemic metabolic dysfunction. However, the relation clinical phenotypes depot-specific not well examined in human obesity.To characterize inflammatory status subcutaneous and visceral fat depots, as assessed by presence macrophage crown-like structures (CLS) a hallmark chronic inflammation, determine insulin resistance abnormalities fat.We collected simultaneously from (omental...
The purpose of this study was to characterize the relationship between adipose tissue phenotype and depot-specific microvascular function in fat.In 30 obese subjects (age 42±11 years, body mass index 46±11 kg/m(2)) undergoing bariatric surgery, we intraoperatively collected visceral subcutaneous characterized phenotypes. We assessed vasomotor microvasculature using videomicroscopy small arterioles (75-250 μm) isolated from different fat compartments. Endothelium-dependent,...
Background— Experimental studies suggest that visceral adiposity and adipose tissue dysfunction play a central role in obesity-related cardiometabolic complications. Impaired angiogenesis fat has been implicated the development of hypoxia, capillary rarefaction, inflammation, metabolic dysregulation, but pathophysiological mechanisms remain unknown. In this study, we examined novel antiangiogenic isoform vascular endothelial growth factor-A (VEGF-A), VEGF-A 165 b, human obesity. Methods...
Background The American Heart Association's framework "ideal cardiovascular health" (CVH) focuses on modifiable risk factors to reduce disease (CVD). Metabolomics provides important pathobiological insights into and CVD development. We hypothesized that metabolomic signatures associate with CVH status, metabolites, at least partially, mediate the association of score atrial fibrillation (AF) heart failure (HF). Methods Results studied 3056 adults in FHS (Framingham Study) cohort evaluate...
Accumulation of macrophages and T cells within crown-like structures (CLS) in subcutaneous adipose tissue predicts disease severity obesity-related insulin resistance (OIR). Although rodent data suggest the B cell is an important feature these lesions, have not been described human CLS. In order to identify CLS (sCLS) obese subjects determine whether presence predict resistance, we examined archived samples omental fat from 32 men women related findings clinical parameters. Using...
There is growing recognition that adipose tissue-derived proatherogenic mediators contribute to obesity-related cardiovascular disease. We sought characterize regional differences in perivascular tissue (PVAT) phenotype relation atherosclerosis susceptibility. Approach and Results: examined thoracic PVAT samples 34 subjects (body mass index 32±6 kg/m2, age 59±11 years) undergoing valvular, aortic, or coronary artery bypass graft surgeries performed transcriptomic characterization using...
The accumulation of visceral adiposity is strongly associated with systemic inflammation and increased cardiometabolic risk. WNT5A, a non-canonical WNT ligand, has been shown to promote adipose tissue insulin resistance in animal studies. Among other pathways, WNT5A activates planar cell polarity (PCP) signaling. current study investigated the potential contribution WNT5A/PCP signaling (VAT) metabolic dysfunction individuals obesity. VAT subcutaneous (SAT) samples obtained from subjects...
Obesity, particularly visceral adiposity, has been linked to mitochondrial dysfunction and increased oxidative stress, which have suggested as mechanisms of insulin resistance. The mechanism(s) behind this remains incompletely understood. In study, we hypothesized that complex II plays a role in impaired sensitivity adipose tissue subjects with obesity. We obtained subcutaneous biopsies from 43 obesity (body mass index ≥ 30 kg/m 2 ) during planned bariatric surgery. Compared tissue,...
Increased visceral adiposity has been closely linked to insulin resistance, endothelial dysfunction, and cardiometabolic disease in obesity, but pathophysiological mechanisms are poorly understood. We sought investigate of vascular resistance by characterizing depot-specific responses gain evidence that altered functionality transcription factor forkhead box O-1 (FOXO-1) may play an important role obesity-related dysfunction.We intraoperatively collected paired subcutaneous adipose tissue...
Experimental studies have suggested that Wingless-related integration site 5A (WNT5A) is a proinflammatory secreted protein associated with metabolic dysfunction in obesity. Impaired angiogenesis fat depots has been implicated the development of adipose tissue capillary rarefaction, hypoxia, inflammation, and dysfunction. We recently demonstrated impaired overexpression antiangiogenic factor VEGF-A
Obesity is associated with the development of vascular insulin resistance; however, pathophysiological mechanisms are poorly understood. We sought to investigate role WNT5A-JNK in regulation insulin-mediated vasodilator responses human adipose tissue arterioles prone endothelial dysfunction. In 43 severely obese (BMI 44±11 kg/m 2 ) and five metabolically normal non-obese 26±2 subjects, we isolated from subcutaneous visceral fat during planned surgeries. Using videomicroscopy, examined...
The purpose of this study was to determine whether cyclooxygenase inhibition improves vascular dysfunction adipose microvessels from obese humans.In 20 subjects (age 37 ± 12 years, BMI 47 8 kg/m²), subcutaneous and visceral fat were collected during bariatric surgery characterized for depot-specific gene expression, endothelial cell phenotype, microvascular function. Vasomotor function assessed in response endothelium-dependent agonists using videomicroscopy small arterioles fat.Arterioles...
<h3>Importance</h3> Bariatric surgical weight loss is associated with reduced cardiovascular mortality; however, the mechanisms underlying this association are incompletely understood. <h3>Objectives</h3> To identify variables vascular remodeling after bariatric surgery and to examine how sex, race, metabolic status microvascular macrovascular outcomes. <h3>Design, Setting, Participants</h3> This population-based longitudinal cohort included 307 individuals who underwent surgery....
Background. Dysregulated lipolysis has been implicated in mechanisms of cardiometabolic disease and inflammation obesity. Purpose . We sought to examine the effect bariatric weight loss on adipose tissue lipolytic gene expression their relationship systemic metabolic parameters obese subjects. Methods/Results biopsied subcutaneous 19 individuals (BMI 42 ± 5 kg/m 2 , 79% female) at baseline after a mean period 8 months (range 3–15 months) following surgery. performed mRNA proteins involved...