CB1 blockade potentiates down-regulation of lipogenic gene expression in perirenal adipose tissue in high carbohydrate diet-induced obesity
| Autor: | Ana Luisa Gavito, Fernando Rodríguez de Fonseca, Sergio Arrabal, Patricia Rivera, Dolores Bautista, Ana Martínez, Miguel Romero-Cuevas, Juan Suárez, Francisco Javier Pavón, Antonia Serrano, Margarita Vida, Elena Baixeras |
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| Přispěvatelé: | [Vida,M, Rivera,P, Gavito,AL, Suárez,J, Pavón,FJ, Arrabal,S, Romero-Cuevas,M, Rodriguez de Fonseca,F, Serrano.A] Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain. [Baixeras,E] Unidad de Gestión Clínica de Medicina Interna, Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain. [Bautista,D] Unidad de Gestión Clínica de Anatomía Patológica, Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain. [Vida,M, Bautista,D, Rodríguez de Fonseca,F, Serrano,A, Baixeras,E] Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain. [Martínez,A] Instituto de Química Médica Lora Tamayo, Consejo Superior de Investigaciones Científicas. Madrid, Spain. [Vida,M, RiveraP, Rodríguez de Fonseca, Serrano,A] CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Santiago de Compostela, Spain., This work was supported by Grants: from the Spanish Institute of Health ‘‘Carlos III (PI061109, CP12/03109, CIBERobn EU-ERDF-CB06/03/1008), from the Andalusian Ministry of Health (PI0552), from Andalusian Ministry of Economy, Innovation, Science and Employment EU-ERDF (CTS-8221 and CTS-433), from Spanish Ministry of Science and Innovation (SAF2010-20521), from European Union’s 7th Framework Programme (Health- F2-2008-223713, REPROBESITY). I3SNS Program of the Spanish National Health System of Spanish Ministry of Science and Innovation. |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
Time Factors Anatomy::Urogenital System::Urinary Tract::Kidney [Medical Subject Headings] Technology Industry Agriculture::Food and Beverages::Food::Dietary Carbohydrates [Medical Subject Headings] Phenomena and Processes::Physical Phenomena::Time::Time Factors [Medical Subject Headings] Obesidad Adipose tissue lcsh:Medicine Riñón Phenomena and Processes::Physiological Phenomena::Body Constitution::Body Weights and Measures::Body Size::Body Weight [Medical Subject Headings] Signal transduction ERK signaling cascade Kidney Phenomena and Processes::Physiological Phenomena::Body Constitution::Body Weights and Measures::Body Size::Body Weight::Overweight::Obesity [Medical Subject Headings] Biochemistry Phenomena and Processes::Physiological Phenomena::Physiological Processes::Pharmacological Processes::Down-Regulation [Medical Subject Headings] Chemicals and Drugs::Amino Acids Peptides and Proteins::Proteins::Membrane Proteins::Receptors Cell Surface::Receptors G-Protein-Coupled::Receptors Cannabinoid::Receptor Cannabinoid CB1 [Medical Subject Headings] Molecular cell biology 0302 clinical medicine Piperidines Receptor Cannabinoid CB1 Gene expression Organisms::Eukaryota::Animals [Medical Subject Headings] Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats::Rats Wistar [Medical Subject Headings] lcsh:Science 0303 health sciences Multidisciplinary Signaling cascades food and beverages Neurochemistry Animal Models Lipids PKA signaling cascade 3. Good health Lipogenesis Carbohydrate Metabolism lipids (amino acids peptides and proteins) Neurochemicals Research Article medicine.medical_specialty Adipose Tissue White Phenomena and Processes::Metabolic Phenomena::Metabolism::Lipid Metabolism::Lipogenesis [Medical Subject Headings] Tejido adiposo blanco Check Tags::Male [Medical Subject Headings] Down-Regulation 030209 endocrinology & metabolism Biology Diet High-Fat Chemicals and Drugs::Amino Acids Peptides and Proteins::Proteins::Transcription Factors [Medical Subject Headings] Alimentación rica en grasa 03 medical and health sciences Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet::Diet High-Fat [Medical Subject Headings] Model Organisms Downregulation and upregulation Internal medicine Dietary Carbohydrates medicine Animals Lipogénesis Obesity Rats Wistar Liver X receptor Carbohydrate-responsive element-binding protein Transcription factor 030304 developmental biology Body Weight lcsh:R Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Signal Transduction [Medical Subject Headings] Peso corporal Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds 1-Ring::Piperidines [Medical Subject Headings] Lipid Metabolism Rats Sterol regulatory element-binding protein Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats [Medical Subject Headings] Anatomy::Tissues::Connective Tissue::Adipose Tissue::Adipose Tissue White [Medical Subject Headings] Metabolism Endocrinology Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds 1-Ring::Azoles::Pyrazoles [Medical Subject Headings] Carbohidratos dietéticos Pyrazoles Rat lcsh:Q Transcription Factors Neuroscience Endocannabinoids |
| Zdroj: | PLoS ONE, Vol 9, Iss 2, p e90016 (2014) PLoS ONE; Vol 9 PLoS ONE Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 1932-6203 |
| Popis: | De novo lipogenesis and hypercaloric diets are thought to contribute to increased fat mass, particularly in abdominal fat depots. CB1 is highly expressed in adipose tissue, and CB1-mediated signalling is associated with stimulation of lipogenesis and diet-induced obesity, though its contribution to increasing fat deposition in adipose tissue is controversial. Lipogenesis is regulated by transcription factors such as liver X receptor (LXR), sterol-response element binding protein (SREBP) and carbohydrate- responsive-element-binding protein (ChREBP). We evaluated the role of CB 1 in the gene expression of these factors and their target genes in relation to lipogenesis in the perirenal adipose tissue (PrAT) of rats fed a high-carbohydrate diet (HCHD) or a high-fat diet (HFD). Both obesity models showed an up-regulated gene expression of CB1 and Lxrα in this adipose pad. The Srebf-1 and ChREBP gene expressions were down-regulated in HFD but not in HCHD. The expression of their target genes encoding for lipogenic enzymes showed a decrease in diet-induced obesity and was particularly dramatic in HFD. In HCHD, CB1 blockade by AM251 reduced the Srebf-1 and ChREBP expression and totally abrogated the remnant gene expression of their target lipogenic enzymes. The phosphorylated form of the extracellular signal-regulated kinase (ERK-p), which participates in the CB1-mediated signalling pathway, was markedly present in the PrAT of obese rats. ERK-p was drastically repressed by AM251 indicating that CB1 is actually functional in PrAT of obese animals, though its activation loses the ability to stimulate lipogenesis in PrAT of obese rats. Even so, the remnant expression levels of lipogenic transcription factors found in HCHD-fed rats are still dependent on CB1 activity. Hence, in HCHD-induced obesity, CB1 blockade may help to further potentiate the reduction of lipogenesis in PrAT by means of inducing down-regulation of the ChREBP and Srebf-1 gene expression, and consequently in the expression of lipogenic enzymes. |
| Databáze: | OpenAIRE |
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