Elaidyl-sulfamide, an oleoylethanolamide-modelled PPARα agonist, reduces body weight gain and plasma cholesterol in rats
| العنوان: | Elaidyl-sulfamide, an oleoylethanolamide-modelled PPARα agonist, reduces body weight gain and plasma cholesterol in rats |
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| المؤلفون: | Nieves Fresno, Fernando Rodríguez de Fonseca, Antonia Serrano, Ruth Pérez-Fernández, Francisco Javier Pavón, Carolina Cano, Juan Decara, Margarita Vida, Patricia Rivera, Juan Suárez, Miguel Romero-Cuevas, Manuel Macias-Gonzalez |
| المصدر: | Disease Models & Mechanisms, Vol 5, Iss 5, Pp 660-670 (2012) Disease Models & Mechanisms |
| بيانات النشر: | The Company of Biologists, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Blood Glucose, Male, Models, Molecular, Medicine (miscellaneous), Adipose tissue, Peroxisome proliferator-activated receptor, lcsh:Medicine, Oleic Acids, White adipose tissue, Ligands, Weight Gain, Oleoylethanolamide, chemistry.chemical_compound, 0302 clinical medicine, Adipose Tissue, Brown, Immunology and Microbiology (miscellaneous), Brown adipose tissue, Insulin, Oxazoles, chemistry.chemical_classification, Sulfonamides, 0303 health sciences, Thermogenesis, 3. Good health, Solutions, Cholesterol, medicine.anatomical_structure, Liver, Taste, Protein Binding, Research Article, lcsh:RB1-214, medicine.medical_specialty, Adipose Tissue, White, Neuroscience (miscellaneous), Biology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Internal medicine, medicine, lcsh:Pathology, Animals, Humans, PPAR alpha, 030304 developmental biology, Gene Expression Profiling, lcsh:R, Hydrogen Bonding, Lipid metabolism, Feeding Behavior, Glucose Tolerance Test, Amides, Rats, Endocrinology, Gene Expression Regulation, chemistry, Tyrosine, Insulin Resistance, 030217 neurology & neurosurgery |
| الوصف: | Summary We have modelled elaidyl-sulfamide (ES), a sulfamoyl analogue of oleoylethanolamide (OEA). ES is a lipid mediator of satiety that works through the peroxisome proliferator-activated receptor alpha (PPARα). We have characterised the pharmacological profile of ES (0.3-3 mg/kg) by means of in silico molecular docking to the PPARα receptor, in vitro transcription through PPARα and in vitro and in vivo administration to obese rats. ES interacts with the PPARα binding site in a similar way to OEA, is capable of activating PPARα and also reduces feeding in a dose-dependent manner when administered to food-deprived rats. When ES was given to obese male rats for 7 days, it reduced feeding and weight gain, lowered plasma cholesterol and reduced the plasmatic activity of transaminases, indicating a clear improvement of hepatic function. This pharmacological profile is associated with the modulation of both cholesterol and lipid metabolism regulatory genes, including the sterol response element-binding proteins SREBF1/2 and their regulatory proteins INSIG1/2 in liver and white adipose tissues. ES treatment induced the expression of thermogenic regulatory genes, including the uncoupling proteins UCP1/2/3 in brown adipose tissue and UCP3 in white adipose tissue. However, its chronic administration resulted in hyperglycaemia and insulin resistance, which represent a constraint for its potential clinical development. |
| اللغة: | English |
| تدمد: | 1754-8411 1754-8403 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::678e125f0b45c9d83354d5adcab5a77dTest http://dmm.biologists.org/content/5/5/660Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....678e125f0b45c9d83354d5adcab5a77d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17548411 17548403 |
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