Vida, MargaritaRivera, PatriciaGavito, Ana LuisaSuárez, JuanPavón, Francisco JavierArrabal, SergioRomero-Cuevas, MiguelBautista, DoloresMartínez, AnaRodríguez de Fonseca, FernandoSerrano, AntoniaBaixeras, Elena2015-09-092015-09-092014-02-25Vida M, Rivera P, Gavito AL, Suárez J, Pavón FJ, Arrabal S, et al. CB1 blockade potentiates down-regulation of lipogenic gene expression in perirenal adipose tissue in high carbohydrate diet-induced obesity. PLoS ONE. 2014; 9(2):e90016http://hdl.handle.net/10668/1976Journal Article; Research Support, Non-U.S. Gov't;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 CB1 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.enTejido adiposo blancoAlimentación rica en grasaCarbohidratos dietéticosRiñónLipogénesisPeso corporalObesidadMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Body Constitution::Body Weights and Measures::Body Size::Body WeightMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet::Diet, High-FatMedical Subject Headings::Technology, Industry, Agriculture::Food and Beverages::Food::Dietary CarbohydratesMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Physiological Processes::Pharmacological Processes::Down-RegulationMedical Subject Headings::Anatomy::Urogenital System::Urinary Tract::KidneyMedical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Lipid Metabolism::LipogenesisMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Body Constitution::Body Weights and Measures::Body Size::Body Weight::Overweight::ObesityMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::PiperidinesMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Azoles::PyrazolesMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::RatsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats::Rats, WistarMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, G-Protein-Coupled::Receptors, Cannabinoid::Receptor, Cannabinoid, CB1Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Signal TransductionMedical Subject Headings::Phenomena and Processes::Physical Phenomena::Time::Time FactorsMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription FactorsMedical Subject Headings::Anatomy::Tissues::Connective Tissue::Adipose Tissue::Adipose Tissue, Whiteresearch article24587189open access10.1371/journal.pone.00900161932-6203PMC3934980