A5077042210- Peroxisome Proliferator-Activated Receptors
- Cholesterol and Lipid Metabolism
- Adipose Tissue and Metabolism
- Histone Deacetylase Inhibitors Research
- Drug Transport and Resistance Mechanisms
- Nuclear Receptors and Signaling
- Metabolism, Diabetes, and Cancer
- Eicosanoids and Hypertension Pharmacology
- Cancer, Hypoxia, and Metabolism
- Receptor Mechanisms and Signaling
- Protein Degradation and Inhibitors
- Inflammatory mediators and NSAID effects
- Liver Disease Diagnosis and Treatment
- Adipokines, Inflammation, and Metabolic Diseases
- Lipid metabolism and biosynthesis
- Liver physiology and pathology
- Subtitles and Audiovisual Media
- RNA Interference and Gene Delivery
- Sirtuins and Resveratrol in Medicine
- RNA and protein synthesis mechanisms
- Inflammation biomarkers and pathways
- Heme Oxygenase-1 and Carbon Monoxide
- Lipid metabolism and disorders
- Pharmacogenetics and Drug Metabolism
- Neonatal Respiratory Health Research
Centro Nacional de Biotecnología
2021-2023
Consejo Superior de Investigaciones Científicas
2023
Scripps Research Institute
2011-2020
Molecular Medicine Research Institute
2018
Dulbecco Telethon Institute
2013
University of Milan
2004-2012
University of Naples Federico II
2008
University of L'Aquila
2008
Genomics Institute of the Novartis Research Foundation
2006
Texas A&M University System
2006
Chromatin modifications are sensitive to environmental and nutritional stimuli. Abnormalities in epigenetic regulation associated with metabolic disorders such as obesity diabetes that often linked defects oxidative metabolism. Here, we evaluated the potential of class-specific synthetic inhibitors histone deacetylases (HDACs), central chromatin-remodeling enzymes, ameliorate dysfunction. Cultured myotubes primary brown adipocytes treated a class I-specific HDAC inhibitor showed higher...
Extracts of the hops plant have been shown to reduce weight and insulin resistance in rodents humans, but elucidation mechanisms responsible for these benefits has hindered by use heterogeneous hops-derived mixtures. Because hop extracts are used as flavoring agents their bitter properties, we hypothesized that taste receptors (Tas2rs) could be mediating beneficial effects metabolic disease. Studies exposure cultured enteroendocrine cells tastants can stimulate release hormones, including...
The peroxisome proliferator-activated receptors (PPARs) are transcriptional regulators of glucose and lipid metabolism. They activated by natural ligands, such as fatty acids, also targets synthetic antidiabetic hypolipidemic drugs. By using cell-based reporter assays, we studied the transactivation activity two enantiomeric ureidofibrate-like derivatives. In particular, show that R-enantiomer, (R)-1, is a full agonist PPARgamma, whereas S-enantiomer, (S)-1, less potent partial agonist. Most...
The peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors regulating glucose and lipid metabolism. search for new PPAR ligands with reduced adverse effects respect to the marketed antidiabetic agents thiazolidinediones (TZDs) dual-agonists glitazars is highly desired. We report crystal structure activity of two enantiomeric forms a clofibric acid analogue, respectively complexed ligand-binding domain (LBD) PPARgamma, provide an explanation on...
Abstract Background Recent data highlighted the role of nuclear receptors in transcriptional regulation limiting enzyme bile acid synthesis, cholesterol 7α‐hydroxylase, cellular and animal models. This study was designed to analyze effects age on 7α‐hydroxylase related receptor expression human livers. Design Surgical liver biopsies were obtained 23 patients requiring operation gastrointestinal tract. mRNA levels co‐activators assayed by quantitative real‐time RT‐PCR. Serum...
The transcription of the gene (CYP7A1) encoding cholesterol 7alpha-hydroxylase, a key enzyme in homeostasis, is repressed by bile acids via multiple mechanisms involving members nuclear receptor superfamily. Here, we describe regulatory mechanism that can be exploited for modulating acid synthesis. By dissecting CYP7A1 transcription, found stimulate sequential recruitment histone deacetylases (HDACs) 7, 3, and 1, corepressor SMRTalpha (silencing mediator retinoid thyroid receptors-alpha)...
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that govern lipid and glucose homeostasis playing a central role in cardiovascular diseases, obesity, diabetes. Medications targeted to PPARs have been established treat hyperlipidemia (fibrates) insulin resistance (glitazones). Thus, there is significant interest developing new specific ligands for these receptors. Here, we present the results of screening PPARα PPARγ. Optical isomers chiral...
Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant myopathy with a strong epigenetic component. It associated deletion of macrosatellite repeat leading to over-expression the nearby genes. Among them, we focused on FSHD region gene 1 (FRG1) since its in mice, Xenopus laevis and Caenorhabditis elegans, leads dystrophy-like defects, suggesting that FRG1 plays relevant role muscle biology. Here show that, when over-expressed, binds interferes activity histone...
Abstract Background Cholesterol cholelithiasis (gallstone disease) is a common disease in the Western world. The aim of present study was to analyze hepatic expression number nuclear receptors involved bile acid metabolism human cholesterol gallstone disease. Materials and methods Surgical liver biopsies were obtained from 11 patients with untreated nine gallstone‐free subjects; mRNA levels 7α‐hydroxylase (CYP7A1) related coactivators assayed by quantitative real‐time RT‐PCR. Results No...
Objective: In a phase II clinical trial in nine obese, insulin-resistant humans, we observed that treatment with KDT501, novel isohumulone drug, increased total and high molecular weight adiponectin plasma. The objective was to determine whether KDT501 secretion from subcutaneous white adipose tissue (SC WAT) the underlying mechanism(s). Methods: Nine obese participants either prediabetes or normal glucose tolerance plus three features of metabolic syndrome were part study. SC WAT biopsies...
Respiratory disorders caused by allergy have been associated to bronchiolar inflammation leading life-threatening airway narrowing. However, whether causes alveolar dysfunction contributing the pathology of allergic asthma remains unaddressed. To explore that might contribute asthma, structural and functional alterations were analyzed during house dust mite (HDM)-induced in mice, flow cytometry, light electron microscopy, monocyte transfer experiments, assessment intra-alveolarly-located...
A series of [4-(2H-1,2,3-benzotriazol-2-yl)phenoxy]alkanoic acids has been synthesized and tested as agonists Peroxisome Proliferator-Activated Receptor (PPAR) alpha, gamma, delta. Three compounds displayed 56 to 96% maximal activity the reference drug Wy-14643 on PPARalpha, two these, i.e., 1 5, exhibited also moderate either PPARgamma or delta with efficacy equal 50% 46% that rosiglitazone GW 501516, respectively. Thus, 5 represent interesting starting point for preparing novel agents...