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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Inhibition of cannabinoid CB1 receptor upregulates Slc2a4 expression via nuclear factor-kappa B and sterol regulatory element-binding protein-1 in adipocytes

Texto completo
Autor(es):
Furuya, D. T. [1] ; Poletto, A. C. [1] ; Freitas, H. S. [1] ; Machado, U. F. [1]
Número total de Autores: 4
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Dept Physiol & Biophys, Inst Biomed Sci, BR-05508900 Sao Paulo - Brazil
Número total de Afiliações: 1
Tipo de documento: Artigo Científico
Fonte: JOURNAL OF MOLECULAR ENDOCRINOLOGY; v. 49, n. 2, p. 97-106, OCT 2012.
Citações Web of Science: 15
Resumo

Evidences have suggested that the endocannabinoid system is overactive in obesity, resulting in enhanced endocannabinoid levels in both circulation and visceral adipose tissue. The blockade of cannabinoid receptor type 1 (CB1) has been proposed for the treatment of obesity. Besides loss of body weight, CB1 antagonism improves insulin sensitivity, in which the glucose transporter type 4 (GLUT4) plays a key role. The aim of this study was to investigate the modulation of GLUT4-encoded gene (Slc2a4 gene) expression by CB1 receptor. For this, 3T3-L1 adipocytes were incubated in the presence of a highly selective CB1 receptor agonist (1 mu M arachidonyl-2'-chloroethylamide) and/or a CB1 receptor antagonist/inverse agonist (0.1, 0.5, or 1 mu M AM251, 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyra zole-3-carboxamide). After acute (2 and 4 h) and chronic (24 h) treatments, cells were harvested to evaluate: i) Slc2a4, Cnr1 (CB1 receptor-encoded gene), and Srebf1 type a (SREBP-1a type-encoded gene) mRNAs (real-time PCR); ii) GLUT4 protein (western blotting); and iii) binding activity of nuclear factor (NF)-kappa B and sterol regulatory element-binding protein (SREBP)-1 specifically in the promoter of Slc2a4 gene (electrophoretic mobility shift assay). Results revealed that both acute and chronic CB1 receptor antagonism greatly increased (similar to 2.5-fold) Slc2a4 mRNA and protein content. Additionally, CB1-induced upregulation of Slc2a4 was accompanied by decreased binding activity of NF-kappa B at 2 and 24 h, and by increased binding activity of the SREBP-1 at 24 h. In conclusion, these findings reveal that the blockade of CB1 receptor markedly increases Slc2a4/GLUT4 expression in adipocytes, a feature that involves NF-kappa B and SREBP-1 transcriptional regulation. Journal of Molecular Endocrinology (2012) 49, 97-106 (AU)

Processo FAPESP: 08/09194-4 - Modulação da proteína transportadora de glicose glut4 pelo receptor canabinóide cb1 em adipócitos 3t3-l1 e tecido adiposo visceral de camungos obesos
Beneficiário:Daniela Tomie Furuya
Linha de fomento: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 07/50554-1 - Transportadores de glicose e Diabetes mellitus: contribuição ao conhecimento da regulação da glicemia e do desenvolvimento de complicações
Beneficiário:Ubiratan Fabres Machado
Linha de fomento: Auxílio à Pesquisa - Temático