A5066357356- Mitochondrial Function and Pathology
- Adipose Tissue and Metabolism
- ATP Synthase and ATPases Research
- Metabolism, Diabetes, and Cancer
- Cardiovascular Function and Risk Factors
- Pulmonary Hypertension Research and Treatments
- Cancer, Hypoxia, and Metabolism
- Diet and metabolism studies
- Retinal Development and Disorders
- Pancreatic function and diabetes
- Genetics, Aging, and Longevity in Model Organisms
- Heat shock proteins research
- Drug Transport and Resistance Mechanisms
- Liver Disease Diagnosis and Treatment
- bioluminescence and chemiluminescence research
- Adenosine and Purinergic Signaling
- Autophagy in Disease and Therapy
- Hereditary Neurological Disorders
- Regulation of Appetite and Obesity
- Iron Metabolism and Disorders
- Cardiac Ischemia and Reperfusion
- Extracellular vesicles in disease
- Adipokines, Inflammation, and Metabolic Diseases
- Apelin-related biomedical research
- Amino Acid Enzymes and Metabolism
Florida International University
2022-2025
Fraternal Order of Eagles
2014-2020
University of Iowa
2014-2020
University of Nebraska–Lincoln
2017
University of Utah
2008-2017
University of Colorado Anschutz Medical Campus
2017
Washington University in St. Louis
2017
University of Alabama at Birmingham
2017
University of Freiburg
2017
Cardiac lipotoxicity, characterized by increased uptake, oxidation, and accumulation of lipid intermediates, contributes to cardiac dysfunction in obesity diabetes mellitus. However, mechanisms linking overload mitochondrial are incompletely understood.To elucidate the for adaptations postnatal hearts vivo.Using a transgenic mouse model lipotoxicity overexpressing ACSL1 (long-chain acyl-CoA synthetase 1) cardiomyocytes, we show that modestly myocardial fatty acid uptake leads structural...
The receptors for IGF-I (IGF-IR) and insulin (IR) have been implicated in physiological cardiac growth, but it is unknown whether IGF-IR or IR signaling are critically required. We generated mice with cardiomyocyte-specific knockout of (CIGF1RKO) compared them receptor (CIRKO) response to 5 wk exercise swim training. Cardiac development was normal CIGF1RKO mice, the hypertrophic prevented. In contrast, despite reduced baseline heart size, CIRKO hearts preserved. Exercise increased content...
OBJECTIVE To elucidate the molecular basis for mitochondrial dysfunction, which has been implicated in pathogenesis of diabetes complications. RESEARCH DESIGN AND METHODS Mitochondrial matrix and membrane fractions were generated from liver, brain, heart, kidney wild-type type 1 diabetic Akita mice. Comparative proteomics was performed using label-free proteome expression analysis. state 3 respirations ATP synthesis measured, morphology evaluated by electron microscopy. Expression genes that...
Significance Mitochondrial Ca 2+ is a fundamental signal that allows for adaptation to physiological stress but liability during ischemia-reperfusion injury in heart. On one hand, mitochondrial entry coordinates energy supply and demand myocardium by increasing the activity of matrix dehydrogenases augment ATP production oxidative phosphorylation. other inhibiting overload promulgated as therapeutic approach preserve myocardial tissue following injury. We developed new mouse model...
OBJECTIVE Excess tissue iron levels are a risk factor for diabetes, but the mechanisms underlying association incompletely understood. We previously published that mice and humans with form of hereditary overload, hemochromatosis, exhibit loss β-cell mass. This effect by itself is not sufficient, however, to fully explain diabetes phenotype associated all forms overload. RESEARCH DESIGN AND METHODS therefore examined glucose fatty acid metabolism hepatic production in vivo vitro mouse model...
Autophagy is a catabolic process involved in maintaining energy and organelle homeostasis. The relationship between obesity the regulation of autophagy cell type specific. Despite adverse consequences on cardiac structure function, contribution altered response to fatty acid overload incompletely understood. Here, we report suppression autophagosome clearance activation NADPH oxidase (Nox)2 both high fat-fed murine hearts palmitate-treated H9C2 cardiomyocytes (CMs). Defective secondary...
Excessive mitochondrial fission and a shift to Warburg phenotype are hallmarks of pulmonary hypertension (PH), although the mechanistic link between these processes remains unclear. We show that in arterial endothelial cells (PAEC), Drp1 overexpression induces increases glycolytic ATP production glycolysis. This is due reactive oxygen species (mito-ROS)-mediated activation hypoxia-inducible factor-1α (HIF-1α) signaling, this linked hydrogen peroxide (H2O2)-mediated inhibition prolyl...
Background Increased glucose transporter 1 ( GLUT1 ) expression and utilization that accompany pressure overload‐induced hypertrophy POH are believed to be cardioprotective. Moreover, it has been shown lifelong transgenic overexpression of in the heart prevents cardiac dysfunction after aortic constriction. The relevance this model clinical practice is unclear because life‐long duration increased metabolism. Therefore, we sought determine if a short‐term increase ‐mediated myocardial uptake...
Small heterodimer partner (SHP) is an epigenetically regulated nuclear transcriptional repressor that suppresses the development of liver cancer by inhibiting cellular growth. Here we report a novel cytoplasmic function SHP through its regulation mitochondrial activity. pivotal cell death receptor targets mitochondria, where it binds with Bcl-2, disrupts Bcl-2/Bid interaction, and induces cytochrome c release. The apoptosis inducer AHPN {retinoid...
ob/ob and db/db mice manifest myocardial hypertrophy, insulin resistance, altered substrate utilization, mitochondrial dysfunction, lipid accumulation. This study was designed to determine the contribution of central peripheral leptin signaling metabolism function in absence diabetes morbid obesity.Male (aged 4 weeks) were caloric restricted by pairfeeding a leptin-treated group. In addition determining glucose tolerance circulating concentrations, determined saponin-permeabilized cardiac...
Insulin/IGF-I signaling regulates the metabolism of most mammalian tissues including pancreatic islets. To dissect mechanisms linking insulin with mitochondrial function, we first identified a mitochondria-tethering complex in β-cells that included glucokinase (GK), and pro-apoptotic protein, BADS. Mitochondria isolated from derived β-cell specific receptor knockout (βIRKO) mice exhibited reduced BADS, GK protein kinase A complex, attenuated function. Similar alterations were evident islets...
It is well-established that mitochondrial dysfunction plays a critical role in the development of pulmonary hypertension (PH). However, molecular mechanisms and how individual electron transport complexes (ETC) may be affected are poorly understood. In this study, we identified decreased ETC Complex I activity assembly linked these changes to disrupted bioenergetics arterial endothelial cells (PAECs) isolated from lamb model PH with increased blood flow (Shunt). These derangements were...
Mechanistic target of rapamycin (mTOR) is essential for cardiac development, growth, and function, but the role mTOR in regulation metabolism mitochondrial respiration not well established. This study sought to determine bioenergetics mice with inducible deletion adult heart. Doxycycline-inducible cardiac-specific mTOR-deficient were generated by crossing doxycycline-inducible tetO-Cre harboring floxed alleles. Deletion reduced mTORC1 mTORC2 signaling after vivo insulin stimulation. Maximum...
OBJECTIVE To identify metabolic pathways that may underlie susceptibility or resistance to high-fat diet–induced hepatic steatosis. RESEARCH DESIGN AND METHODS We performed comparative transcriptomic analysis of the livers A/J and C57Bl/6 mice, which are, respectively, resistant susceptible hepatosteatosis obesity. Mice from both strains were fed a normal chow diet for 2, 10, 30 days, data analyzed by time-dependent gene set enrichment analysis. Biochemical mitochondrial respiration was...
Objective Multiplexed metabolic phenotyping systems are available from multiple commercial vendors, and each system includes unique design features. Although expert opinion supports strengths weaknesses of design, empirical data carefully controlled studies to test the biological impact differences lacking. Methods Wild‐type C57BL/6J mice both sexes underwent in OxyMax (Columbus Instruments International) Promethion (Sable Systems located within same room a newly constructed animal research...
The disruption of mitochondrial dynamics has been identified in cardiovascular diseases, including pulmonary hypertension (PH), ischemia-reperfusion injury, heart failure, and cardiomyopathy. Mitofusin 2 (Mfn2) is abundantly expressed vasculature cells at the outer membrane to modulate fusion. Previously, we have reported reduced levels Mfn2 fragmented mitochondria arterial endothelial (PAECs) isolated from a sheep model PH induced by over-circulation restoring normalized function. In this...