A5002172845- Adipose Tissue and Metabolism
- Adipokines, Inflammation, and Metabolic Diseases
- Receptor Mechanisms and Signaling
- Heart Failure Treatment and Management
- Pharmacological Effects and Assays
- Regulation of Appetite and Obesity
- Diet and metabolism studies
- Neuropeptides and Animal Physiology
- Peroxisome Proliferator-Activated Receptors
- Lipid metabolism and biosynthesis
- Muscle metabolism and nutrition
- Fatty Acid Research and Health
- Mitochondrial Function and Pathology
- Hormonal Regulation and Hypertension
- Cancer, Stress, Anesthesia, and Immune Response
- Pancreatic function and diabetes
- Cardiovascular Disease and Adiposity
- GDF15 and Related Biomarkers
- Cardiovascular and exercise physiology
- Metabolism, Diabetes, and Cancer
- Sirtuins and Resveratrol in Medicine
- Pulmonary Hypertension Research and Treatments
- Diabetes Treatment and Management
- Estrogen and related hormone effects
- Cardiovascular Function and Risk Factors
Vanderbilt University
2019-2024
Vanderbilt University Medical Center
2019-2024
Nashville Oncology Associates
2024
Discovery Institute
2016-2023
Sanford Burnham Prebys Medical Discovery Institute
2012-2023
Duke Medical Center
2000-2020
Diabetes Australia
2013
Orlando Health
2013
Toxicologie, Pharmacologie et Signalisation Cellulaire
2013
The Hamner Institutes for Health Sciences
2007-2010
The ability of mammals to resist body fat accumulation is linked their expand the number and activity "brown adipocytes" within white depots. Activation β-adrenergic receptors (β-ARs) can induce a functional "brown-like" adipocyte phenotype. As cardiac natriuretic peptides (NPs) β-AR agonists are similarly potent at stimulating lipolysis in human adipocytes, we investigated whether NPs could mouse adipocytes acquire brown features, including capacity for thermogenic energy expenditure...
Screening of a human placenta lambda gt11 library has led to the isolation cDNA for beta 1-adrenergic receptor (beta 1AR). Used as probe was genomic clone termed G-21. This clone, which contains an intronless gene putative receptor, previously isolated by virtue its cross hybridization with 2-adrenergic 2AR). The 2.4-kilobase 1AR encodes protein 477 amino acid residues that is 69% homologous avian AR but only 54% 2AR. suggests encoding and evolved from common ancestral gene. RNA blot...
It is well established that catecholamine-stimulated thermogenesis in brown fat requires beta-adrenergic elevations cyclic AMP (cAMP) to increase expression of the uncoupling protein 1 (UCP1) gene. However, little known about downstream components signaling cascade or relevant transcription factor targets thereof. Here we demonstrate cAMP- and kinase A-dependent activation p38 mitogen-activated (MAPK) adipocytes an indispensable step UCP1 gene mice. By phosphorylating activating 2 (ATF-2)...
One of the unique features beta-cells is their relatively low expression many antioxidant enzymes. This could render susceptible to oxidative damage but may also provide a system that sensitive reactive oxygen species as signals. In isolated mouse islets and INS-1(832/13) cells, glucose increases intracellular accumulation H2O2. both models, insulin secretion be stimulated by provision either exogenous H2O2 or diethyl maleate, which raises levels. Provision scavengers, including cell...
Uncoupling protein 2 (UCP2) belongs to the mitochondrial anion carrier family and partially uncouples respiration from ATP synthesis when expressed in recombinant yeast mitochondria. We generated a highly sensitive polyclonal antibody against human UCP2. Its reactivity toward proteins was compared between wild type ucp2(−/−) mice, leading non-ambiguous identification of detected UCP2 spleen, lung, stomach, white adipose tissue. No heart, skeletal muscle, liver, brown The level spleen...
A classic metabolic concept posits that insulin promotes energy storage and adipose expansion, while catecholamines stimulate release of stores by hydrolysis triglycerides through β-adrenergic receptor (βARs) protein kinase (PKA) signaling. Here, we have shown a key hub in the signaling pathway, activation p70 ribosomal S6 (S6K1) mTORC1, is also triggered PKA both mouse human adipocytes. Mice with mTORC1 impairment, either adipocyte-specific deletion Raptor or pharmacologic rapamycin...
We report here the cloning and functional analysis of a novel homologue mitochondrial carriers predominantly expressed in central nervous system referred to as BMCP1 (brain mitochondrialcarrier protein-1). The predicted amino acid sequence this carrier indicates level identity 39, 31, or 30%, toward oxoglutarate carrier, phosphate adenine nucleotide translocator, respectively, 34, 38, 39% with uncoupling proteins UCP1, UCP2, UCP3, respectively. Northern mouse, rat, human tissues demonstrated...
Uncoupling protein 2 (UCP2) maps to a region on distal mouse chromosome 7 that has been linked the phenotypes of obesity and type II diabetes. We recently reported UCP2 expression is increased by high fat feeding in adipose tissue A/J strain mice, which resistant development dietary obesity. More recently, third UCP (UCP3) was identified, expressed largely skeletal muscle brown tissue. The UCP3 genes are located adjacent one another 7. Thus, roles these UCPs both metabolic efficiency linkage...
Because of increasing evidence that G protein-coupled receptors activate multiple signaling pathways, it becomes important to determine the coordination these pathways and their physiological significance. Here we show beta(3)-adrenergic receptor (beta(3)AR) stimulates p38 mitogen-activated protein kinase (p38 MAPK) via PKA in adipocytes cAMP-dependent transcription mitochondrial uncoupling 1 (UCP1) promoter by beta(3)AR requires MAPK. The selective agonist CL316,243 (CL) phosphorylation MAP...
Abstract We have studied cyclic AMP-mediated regulation of the beta 2-adrenergic receptor (beta 2AR). The effects cAMP were assessed in Chinese hamster fibroblast (CHW) cells expressing either wild type human 2AR (CH-beta 2) or mutated forms lacking consensus sequences for phosphorylation by cAMP-dependent protein kinase. Treatment CH-beta 2 with analogue dibutyryl (Bt2cAMP) induces a time-dependent down-regulation number 2AR. This receptors is accompanied decline steady state level mRNA....
Steroid hormones modulate adrenergic receptor responsiveness and number. To investigate the regulation of beta 2-adrenergic gene by glucocorticoids we examined effects synthetic glucocorticoid agonist triamcinolone acetonide on expression receptors in DDT1MF-2 hamster smooth muscle cells. Glucocorticoid treatment (1 X 10(-7) M) produced a 2.2 +/- 0.4-fold (n = 8) increase number (maximum) between 6 12 h) as determined radioligand binding similar catecholamine-stimulated adenylate cyclase...
Fat intake has long been associated with the development of obesity. The studies described herein show that fat adversely affects adipocyte adrenergic receptor (AR) expression and function. As β3AR agonists have shown to acutely reduce adipose tissue mass improve thermogenesis in genetically obese rodents, we examined whether chronic supplementation a high diet highly selectiveβ 3AR agonist, CL316,243, could prevent diet-induced obesity, effect be sustained over prolonged treatment. C57BL/6J...
The adipocyte is like a bank: place to store excess (caloric) cash in times of plenty, and from which one can withdraw savings during "lean times". β-adrenergic receptors are the gateways this mobilization fat be consumed other tissues. This review discusses signaling pathway(s) white brown adipocytes. Studies rodent models show that adipocytes nestled with depots correlate considered key enabling factor resistance diet-induced obesity. Since it now recognized adult humans have adipocytes,...
Both β2- and β3-adrenergic receptors (ARs) are able to activate the extracellular signal-regulated kinase (ERK) pathway. We previously showed that c-Src is required for ERK activation by β2AR it recruited activated through binding of Src homology 3 (SH3) domain proline-rich regions adapter protein β-arrestin1. Despite absence sites phosphorylation β-arrestin binding, β3AR still requires c-Src. Agonist β2AR, but not β3AR, led redistribution green fluorescent protein-tagged plasma membrane. In...
Adipocytes from genetically obese (ob/ob) mice display an impaired response to beta-adrenergic stimulation, but the molecular defects have not been unequivocally identified. The expression and functional activity of beta 1-, 2-, 3-adrenergic receptor (AR) subtypes in white brown adipose tissue lean were compared. Three 3AR transcripts 2.1, 2.6, 3.5 kilobases identified by Northern blotting. All three mRNA species dramatically reduced (by approximately 300-fold) 12-week-old compared those...
In addition to conveying cellular responses an effector molecule, receptors are often themselves regulated by their effectors. We have demonstrated that epinephrine modulates both the rate of transcription beta 2-adrenergic receptor (beta 2AR) gene and steady-state level 2AR mRNA in DDT1MF-2 cells. Short-term (30 min) exposure (100 nM) stimulates transcription, resulting a 3- 4-fold increase levels. These effects mimicked 1 mM N6,O2'-dibutyryladenosine 3',5'-cyclic monophosphate (Bt2cAMP) or...