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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Furuya, D. T. [1] ; Poletto, A. C. [1] ; Freitas, H. S. [1] ; Machado, U. F. [1]
Total Authors: 4
[1] Univ Sao Paulo, Dept Physiol & Biophys, Inst Biomed Sci, BR-05508900 Sao Paulo - Brazil
Total Affiliations: 1
Document type: Journal article
Source: JOURNAL OF MOLECULAR ENDOCRINOLOGY; v. 49, n. 2, p. 97-106, OCT 2012.
Web of Science Citations: 15

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)

FAPESP's process: 07/50554-1 - Glucose transporters and diabetes mellitus: contribution to the knowledge of glycemic control and chronic diseases development
Grantee:Ubiratan Fabres Machado
Support type: Research Projects - Thematic Grants
FAPESP's process: 08/09194-4 - Cannabinoid receptor CB1 modulation of glucose transporter protein GLUT4 in adipocytes 3T3-L1 and visceral adipose tissue of obese mice
Grantee:Daniela Tomie Furuya
Support type: Scholarships in Brazil - Post-Doctorate