A5069855582- Adipose Tissue and Metabolism
- Mitochondrial Function and Pathology
- Autophagy in Disease and Therapy
- Cardiovascular Function and Risk Factors
- Adipokines, Inflammation, and Metabolic Diseases
- Cardiac Ischemia and Reperfusion
- Diet and metabolism studies
- RNA modifications and cancer
- Metabolism, Diabetes, and Cancer
- Cardiovascular Disease and Adiposity
- Adenosine and Purinergic Signaling
- Nitric Oxide and Endothelin Effects
- Cardiomyopathy and Myosin Studies
- Pancreatic function and diabetes
- Muscle metabolism and nutrition
- Cardiac Imaging and Diagnostics
- Heat shock proteins research
- Metabolism and Genetic Disorders
- Endoplasmic Reticulum Stress and Disease
- Muscle Physiology and Disorders
- Congenital heart defects research
- Cancer, Hypoxia, and Metabolism
- Diet, Metabolism, and Disease
- Liver Disease Diagnosis and Treatment
- Apelin-related biomedical research
University of Utah
2016-2025
George E. Wahlen Department of VA Medical Center
2017
Geriatric Research Education and Clinical Center
2017
Diabetes Australia
2004-2016
Idaho State University
2009
Utah State University
2009
Children's Nutrition Research Center at Baylor College of Medicine
2005
Inserm
2002-2003
Université de Bordeaux
2002
Centre National de la Recherche Scientifique
2002
The gene encoding the transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) was targeted in mice. PGC-1alpha null (PGC-1alpha(-/-)) mice were viable. However, extensive phenotyping revealed multi-system abnormalities indicative of an abnormal energy metabolic phenotype. postnatal growth heart and slow-twitch skeletal muscle, organs with high mitochondrial demands, is blunted PGC-1alpha(-/-) With age, develop abnormally increased body...
Pyruvate constitutes a critical branch point in cellular carbon metabolism. We have identified two proteins, Mpc1 and Mpc2, as essential for mitochondrial pyruvate transport yeast, Drosophila, humans. Mpc2 associate to form an ~150-kilodalton complex the inner membrane. Yeast Drosophila mutants lacking MPC1 display impaired metabolism, with accumulation of upstream metabolites depletion tricarboxylic acid cycle intermediates. Loss yeast results defective uptake, silencing or MPC2 mammalian...
In obesity and diabetes, myocardial fatty acid utilization oxygen consumption (MVo(2)) are increased, cardiac efficiency is reduced. Mitochondrial uncoupling has been proposed to contribute these metabolic abnormalities but not directly demonstrated.Oxygen function were determined in db/db hearts perfused with glucose or palmitate. was saponin-permeabilized fibers proton leak kinetics H(2)O(2) generation isolated mitochondria.db/db exhibited reduced increased MVo(2). reactive species (ROS)...
Background— Obesity is a risk factor for cardiovascular disease and strongly associated with insulin resistance type 2 diabetes. Recent studies in obese humans animals demonstrated increased myocardial oxygen consumption (MV̇ o ) reduced cardiac efficiency (CE); however, the underlying mechanisms remain unclear. The present study was performed to determine whether mitochondrial dysfunction uncoupling are responsible performance ob/ob mice. Methods Results— Cardiac function, MV̇ ,...
Diabetes alters cardiac substrate metabolism. The phenotype in insulin-resistant states has not been comprehensively characterized. goal of these studies was to determine whether the hearts leptin-deficient 8-week-old ob/ob mice were able modulate utilization response insulin or changes fatty acid delivery. Ob/ob resistant and glucose intolerant. Insulin signal transduction insulin-stimulated uptake markedly impaired cardiomyocytes. Insulin-stimulated rates glycolysis oxidation 1.5- 1.8-fold...
The microbiota influences obesity, yet organisms that protect from disease remain unknown. During studies interrogating host-microbiota interactions, we observed the development of age-associated metabolic syndrome (MetS). Expansion Desulfovibrio and loss Clostridia were key features associated with obesity in this model are present humans MetS. T cell-dependent events required to prevent disease, replacement rescued obesity. Inappropriate immunoglobulin A targeting increased antagonized...
Background— Diabetes-associated cardiac dysfunction is associated with mitochondrial and oxidative stress, which may contribute to left ventricular dysfunction. The contribution of altered myocardial insulin action, independent changes in systemic metabolism, incompletely understood. present study tested the hypothesis that perinatal loss signaling heart impairs function. Methods Results— In 8-week-old mice cardiomyocyte deletion receptors (CIRKO), inotropic reserves were reduced,...
The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1beta (PGC-1beta) has been implicated in important metabolic processes. A mouse lacking PGC-1beta (PGC1betaKO) was generated and phenotyped using physiological, molecular, bioinformatic approaches. PGC1betaKO mice are generally viable metabolically healthy. Using systems biology, we identified a general defect the expression of genes involved mitochondrial function and, specifically, electron...
Diazoxide opening of the mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channel protects heart against ischemia-reperfusion injury by unknown mechanisms. We investigated mechanisms which mitoK(ATP) may act as an end effector cardioprotection in perfused rat model, permeabilized fibers, and mitochondria. show that diazoxide pretreatment preserves normal low outer membrane permeability to nucleotides cytochrome c these beneficial effects are abolished inhibitor 5-hydroxydecanoate. hypothesize...
Fatty acid-induced mitochondrial uncoupling and oxidative stress have been proposed to reduce cardiac efficiency contribute dysfunction in type 2 diabetes. We hypothesized that may also reduced contractile the 1 diabetic Akita mouse model (Akita).Cardiac function substrate utilization were determined isolated working hearts vivo by echocardiography. Mitochondrial coupling saponin-permeabilized fibers, proton leak kinetics was mitochondria. Hydrogen peroxide production aconitase activity...
AimsDiet-induced obesity is associated with increased myocardial fatty acid (FA) utilization, insulin resistance, and cardiac dysfunction. The study was designed to test the hypothesis that impaired glucose utilization accounts for initial changes in FA metabolism.
High-capacity mitochondrial ATP production is essential for normal function of the adult heart, and evidence emerging that derangements occur in common myocardial diseases. Previous overexpression studies have shown inducible transcriptional coactivator peroxisome proliferator-activated receptor-gamma (PGC)-1alpha capable activating postnatal cardiac myocyte biogenesis. Recently, we generated mice deficient PGC-1alpha (PGC-1alpha(-/-) mice), which survive with modestly blunted growth. To...
Autophagy is a homeostatic cellular process involved in the degradation of long-lived or damaged components. The role autophagy adipogenesis well recognized, but its mature adipocyte function largely unknown. We show that proteins Atg3 and Atg16L1 are required for proper mitochondrial adipocytes. In contrast to previous studies, we found post-developmental ablation causes peripheral insulin resistance independently diet adiposity. Finally, lack reveals cross talk between fat liver, mediated...
Significance Smyd1 is a muscle-specific histone methyltransferase, and its role in the regulation of growth differentiation skeletal cardiac muscle well established. However, despite persistent expression postnatal cardiomyocytes, adult heart largely unknown. We show that regulates energy metabolism heart. Cardiac-specific ablation mouse resulted global downregulation mitochondrial proteins involved oxidative phosphorylation, concurrent with reduced respiration capacity. further demonstrate...
Mitochondrial membrane lipids adapt to exercise or disuse, underscoring an essential role for PE in energy transduction.
Minimizing myocardial ischemia-reperfusion injury has broad clinical implications and is a critical mediator of cardiac surgical outcomes."Ischemic injury" results from restriction in blood supply leading to mismatch between oxygen demand sufficient intensity and/or duration that leads cell necrosis, whereas ischemiareperfusion occurs when restored after period ischemia usually associated with apoptosis (i.e.programmed death).Compared vascular endothelial cells, myocytes are more sensitive...
Obesity and insulin resistance are associated with oxidative stress (OS). The causal role of adipose OS in the pathogenesis these conditions is unknown. To address this issue, we generated mice an adipocyte-selective deletion manganese superoxide dismutase (MnSOD). When fed a high-fat diet (HFD), AdSod2 knockout (KO) exhibited less adiposity, reduced adipocyte hypertrophy, decreased circulating leptin. to diet-induced adiposity was result increased metabolic rate energy expenditure....