A5078782366- Adipose Tissue and Metabolism
- Signaling Pathways in Disease
- Peroxisome Proliferator-Activated Receptors
- Hormonal Regulation and Hypertension
- Heat shock proteins research
- Adipokines, Inflammation, and Metabolic Diseases
- Endoplasmic Reticulum Stress and Disease
- Bone Metabolism and Diseases
- Fibroblast Growth Factor Research
- Bone health and osteoporosis research
- Heme Oxygenase-1 and Carbon Monoxide
- Cytokine Signaling Pathways and Interactions
- Estrogen and related hormone effects
- Cancer, Hypoxia, and Metabolism
- Dermatology and Skin Diseases
- Bone health and treatments
- Lipid metabolism and biosynthesis
- Alcohol Consumption and Health Effects
- Proteoglycans and glycosaminoglycans research
- Metabolism, Diabetes, and Cancer
- Immune Cell Function and Interaction
- Lower Extremity Biomechanics and Pathologies
- Eicosanoids and Hypertension Pharmacology
- PI3K/AKT/mTOR signaling in cancer
- ATP Synthase and ATPases Research
University of Toledo
2010-2024
Hypertension Institute
2014
Abstract Glucocorticoid hormones control diverse physiological processes, including metabolism and immunity, by activating the major glucocorticoid receptor (GR) isoform, GRα. However, humans express an alternative human (h)GRβ, that acts as inhibitor of hGRα to produce a state resistance. Indeed, evidence exists hGRβ contributes many diseases resistance hormone therapy. rigorous testing GRβ contribution has not been possible, because rodents, especially mice, are thought β-isoform. Here, we...
Glucocorticoid receptor-α (GRα) and peroxisome proliferator-activated receptor-γ (PPARγ) regulate adipogenesis by controlling the balance between lipolysis lipogenesis. Here, we show that protein phosphatase 5 (PP5), a nuclear receptor co-chaperone, reciprocally modulates lipometabolic activities of GRα PPARγ. Wild-type PP5-deficient (KO) mouse embryonic fibroblast cells were used to binding PP5 both In response adipogenic stimuli, PP5-KO showed almost no lipid accumulation with reduced...
The peroxisome proliferator-activated receptor gamma (PPARγ) regulates osteoblast and osteoclast differentiation, is the molecular target of thiazolidinediones (TZDs), insulin sensitizers that enhance glucose utilization adipocyte differentiation. However, clinical use TZDs has been limited by side effects including a higher risk fractures bone loss. Here we demonstrate same post-translational modifications at S112 S273, which influence PPARγ pro-adipocytic sensitizing activities, also...
FK506-binding protein-51 (FKBP51) is a molecular cochaperone recently shown to be positive regulator of peroxisome proliferator-activated receptor (PPAR)γ, the master adipocyte differentiation and function. In cellular models adipogenesis, loss FKBP51 not only reduced PPARγ activity but also lipid accumulation, suggesting that knock-out (KO) mice might have insufficient development adipose tissue storage ability. This model was tested by examining wild-type (WT) FKBP51-KO under regular...
Glucocorticoids (GCs) regulate energy supply in response to stress by increasing hepatic gluconeogenesis during fasting. Long-term GC treatment induces steatosis and weight gain. signaling is coordinated via the receptor (GR) GRα, as GRβ isoform lacks a ligand-binding domain. The roles of GR isoforms regulation lipid accumulation unknown. purpose this study was determine whether inhibits actions GCs liver, or enhances accumulation. We show that expression increased adipose liver tissues...
Marrow adipose tissue (MAT) is unique with respect to origin, metabolism, and function. MAT characterized high heterogeneity which correlates skeletal location bone metabolism. This fat depot also highly sensitive various hormonal, environmental, pharmacologic cues it responds changes in volume and/or metabolic phenotype. We have demonstrated previously that has characteristics of both white (WAT) brown (BAT)-like or beige tissue, phenotype attenuated aging diabetes. Here, we extended our...
FK506-binding protein 51 (FKBP51) is a negative regulator of glucocorticoid receptor-α (GRα), although the mechanism unknown. We show here that FKBP51 also chaperone to peroxisome proliferator-activated receptor-γ (PPARγ), which essential for activity, and uncover underlying this differential regulation. In COS-7 cells, overexpression reduced GRα activity at response element-luciferase reporter, while increasing PPARγ proliferator element reporter. Conversely, FKBP51-deficient (knockout)...
Glucocorticoid receptor-α (GRα) and peroxisome proliferator-activated receptor-γ (PPARγ) are critical regulators of adipogenic responses. We have shown that FK506-binding protein 51 (FKBP51) represses the Akt-p38 kinase pathway to reciprocally inhibit GRα but stimulate PPARγ by targeting serine 112 serines 220 234 (GRα). Here, this mechanism is be essential for control cellular adipogenesis. In 3T3-L1 cells, FKBP51 was a prominent marker differentiated state knockdown showed reduced lipid...
Peroxisome proliferator activated receptor gamma (PPARγ) controls both glucose metabolism and an allocation of marrow mesenchymal stem cells (MSCs) toward osteoblast adipocyte lineages. Its activity is determined by interaction with a ligand which directs posttranscriptional modifications PPARγ protein including dephosphorylation Ser112 Ser273, results in acquiring pro-adipocytic insulin-sensitizing activities, respectively. full agonist TZD rosiglitazone (ROSI) decreases phosphorylation...
Although FK506-binding protein 52 (FKBP52) is an established positive regulator of glucocorticoid receptor (GR) activity, in vivo role for FKBP52 control metabolism has not been reported. To address this question, FKBP52(+/-) mice were placed on a high-fat (HF) diet known to induce obesity, hepatic steatosis, and insulin resistance. Tissue profiling wild-type showed high levels the liver but little no expression muscle or adipose tissue, predicting restricted pattern effects metabolism. In...
Renin-angiotensin system (RAS) regulates adipogenic response with adipocyte hypertrophy by increasing oxidative stress. Recent studies have shown the role of peroxisome proliferator-activated receptor-δ (PPARδ) agonist in attenuation angiotensin II-induced The aim this study was to explore a potential mechanistic link between PPARδ and cytoprotective enzyme heme oxygenase-1 (HO-1) elucidate contribution HO-1 regulatory effects agonism an animal model enhanced RAS, Goldblatt 2 kidney 1 clip...
// Gleb Baida 1 , Pankaj Bhalla Alexander Yemelyanov 2 Lance A. Stechschulte 3 Weinian Shou 4 Ben Readhead 5, 6 Joel T. Dudley Edwin R. Sánchez and Irina Budunova Department of Dermatology, Northwestern University, Chicago, IL, USA Medicine, Pulmonary Division, Physiology & Pharmacology, The Center for Diabetes Endocrine Research, University Toledo College Toledo, OH, Wells Pediatric Indiana School Indianapolis, IN, 5 Genetics Genomic Sciences, Icahn Medicine at Mount Sinai, New York, NY,...
Abstract The immunosuppressive ligand FK 506 and the 506‐binding protein FKBP 52 are stimulatory to glucocorticoid receptor ( GR ) activity. Here, we explore underlying mechanism by comparing activity phosphorylation status in response novel nonimmunosuppressive timcodar VX ‐853) presence absence of closely related 51. Using mouse embryonic fibroblast cells MEF s) deficient knockout KO 51 or 52, show decreased at endogenous genes cells, but increased cells. In elevated occurred inhibitory...