A5045559776- Adipose Tissue and Metabolism
- Metabolism, Diabetes, and Cancer
- Cardiovascular Function and Risk Factors
- Mitochondrial Function and Pathology
- Lipid metabolism and biosynthesis
- Pancreatic function and diabetes
- Autophagy in Disease and Therapy
- Diet and metabolism studies
- Calcium signaling and nucleotide metabolism
- Metabolomics and Mass Spectrometry Studies
- Lipid metabolism and disorders
- Cancer, Hypoxia, and Metabolism
- Muscle metabolism and nutrition
- Sphingolipid Metabolism and Signaling
- Diet, Metabolism, and Disease
- Endoplasmic Reticulum Stress and Disease
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Ubiquitin and proteasome pathways
- Cardiac Ischemia and Reperfusion
- Cardiovascular Disease and Adiposity
- Chemotherapy-induced cardiotoxicity and mitigation
- Sirtuins and Resveratrol in Medicine
- GDF15 and Related Biomarkers
- ATP Synthase and ATPases Research
- Adipokines, Inflammation, and Metabolic Diseases
Dalhousie University
2016-2025
Saint John Regional Hospital
2013-2024
Faculty (United Kingdom)
2021
The University of Texas Southwestern Medical Center
2018
Florida College
2017
University of Florida
2017
University of Alberta
2009-2015
Beth Israel Deaconess Medical Center
2009-2014
Harvard University
2009-2014
St Vincents Institute of Medical Research
2014
Cardiovascular physiology and pathophysiology vary dramatically over the course of day. For example, myocardial infarction onset occurs with greater incidence during early morning hours in humans. However, whether tolerance exhibits a time-of-day dependence is unknown.To investigate time day an ischemic insult influences clinically relevant outcomes mice.Wild-type mice were subjected to ischemia/reperfusion (I/R) (45 minutes ischemia followed by 1 or month reperfusion) at distinct times day,...
Emerging evidence suggests that impaired regulation of adipocyte lipolysis contributes to the proinflammatory immune cell infiltration metabolic tissues in obesity, a process is proposed contribute development and exacerbation insulin resistance. To test this hypothesis vivo, we generated mice with adipocyte-specific deletion adipose triglyceride lipase (ATGL), rate-limiting enzyme catalyzing triacylglycerol hydrolysis. In contrast previous models, adiponectin-driven Cre expression was used...
Doxorubicin (DOX) is an effective anti-cancer agent. However, DOX treatment increases patient susceptibility to dilated cardiomyopathy. predisposes cardiomyocytes insult by suppressing mitochondrial energy metabolism, altering calcium flux, and disrupting proteolysis proteostasis. Prior studies have assessed the role of macroautophagy in cardiotoxicity; however, limited examined whether mediates cardiac injury through dysfunctions inter- and/or intra-lysosomal signaling events. Lysosomal...
Oxidative stress due to excessive reactive oxygen species (ROS) and depleted antioxidants such as glutathione (GSH) can give rise apoptotic cell death in acutely diabetic hearts lead heart disease. At present, the source of these cardiac ROS or subcellular site GSH loss [i.e., cytosolic (cGSH) mitochondrial (mGSH) GSH] has not been completely elucidated. With use rotenone (an inhibitor electron transport chain) decrease acute streptozotocin (STZ)-induced rat heart, origin was established....
Triacylglycerol accumulation in insulin target tissues is associated with resistance. Paradoxically, mice global targeted deletion of adipose triglyceride lipase (ATGL), the rate-limiting enzyme triacylglycerol hydrolysis, display improved glucose tolerance and sensitivity despite multiple tissues. To determine molecular mechanisms for this phenotype, ATGL-deficient (ATGL(-/-)) wild-type were injected saline or (10 units/kg, intraperitoneally), then phosphorylation activities key...
Maintenance of circadian alignment between an organism and its environment is essential to ensure metabolic homeostasis. Synchrony achieved by cell autonomous clocks. Despite a growing appreciation the integral relation clocks metabolism, little known regarding direct influence peripheral clock on cellular responses fatty acids. To address this important issue, we utilized genetic model disrupted function specifically in cardiomyocytes vivo (termed cardiomyocyte mutant (CCM)). CCM mice...
Deletion of acetyl CoA carboxylase-2 (Acc2) reportedly causes leanness in the setting hyperphagia. To determine cellular basis for these effects, we generated a mouse model which Acc2 can be selectively deleted by action Cre recombinase. from skeletal muscle, predominant site expression, had no effect on body weight, food intake, or composition. When was inactivated germline, knockout (Acc2KO) mice displayed differences composition, glucose homeostasis as compared to controls chow high fat...
Alterations in myocardial triacylglycerol content have been associated with poor left ventricular function, suggesting that enzymes involved metabolism play an important role regulating contractile function. Myocardial catabolism is mediated by adipose triglyceride lipase (ATGL), which rate limiting for hydrolysis. To address the influence of hydrolysis on energy and we utilized mice cardiomyocyte-specific ATGL overexpression (MHC-ATGL). Biochemical examination MHC-ATGL hearts revealed...
AMP-activated protein kinase (AMPK), an evolutionarily conserved serine-threonine that senses cellular energy status, is activated by stress and neurohumoral stimuli. We investigated the mechanisms which adrenergic signaling alters AMPK activation in vivo. Brown adipose tissue (BAT) highly enriched sympathetic innervation, critical for regulation of homeostasis. performed unilateral denervation BAT wild type (WT) mice to abolish neural input. Six days post-denervation, UCP-1 levels α2...
Although diabetic cardiomyopathy is associated with enhanced intramyocardial triacylglycerol (TAG) levels, the role of TAG catabolizing enzymes in this process unclear. Because hydrolase, adipose triglyceride lipase (ATGL), regulates baseline cardiac metabolism and function, we examined whether alterations cardiomyocyte ATGL impact function during uncontrolled type 1 diabetes. In genetic (Akita) pharmacological (streptozotocin) murine models diabetes, protein expression content were...
Lipid phosphate phosphatase 3 (LPP3) is a membrane-bound enzyme that hydrolyzes lipid phosphates including the bioactive lipid, lysophosphatidic acid (LPA). Elevated circulating LPA production and cellular signaling are implicated in obesity-induced metabolic cardiac dysfunction. Deletion of LPP3 cardiomyocyte increases levels causes heart failure mitochondrial dysfunction mice. To examine influence modulation on cardiomyopathy, we generated mice with cardiomyocyte-specific overexpression...
Glucocorticoids impair insulin sensitivity. Because resistance is closely linked to increased incidence of cardiovascular diseases and given that metabolic abnormalities have been initiation heart failure, we examined the acute effects dexamethasone (DEX) on rat cardiac metabolism. Although injection DEX for 4 h was not associated with hyperinsulinemia, euglycemic-hyperinsulinemic clamp showed a decrease in glucose infusion rate. Rates glycolysis were unaffected, whereas rate oxidation...
The "fuel gauge" AMP-activated protein kinase (AMPK) facilitates ATP production to meet energy demands during metabolic stress. Given the importance of lipoprotein lipase (LPL) in providing hearts with fatty acids (FA), preferred substrate consumed by heart, objective present study was investigate whether activation AMPK influences LPL at its functionally relevant location, coronary lumen. Hearts from overnight-fasted rats were first perfused heparin release LPL, and homogenates these then...