Endocrine Abstracts

Evidences have suggested that the endocannabinoid system is overactive in obesity, resulting in enhanced endocannabinoid levels in both circulation and visceral adipose tissue. The cannabinoid CB1 receptor is expressed in the adipose tissue besides the brain. Few studies in vitro suggest that CB1 activation increases glucose uptake in adipocytes. The objective of the present study was to investigate the CB1 receptor modulation on glucose transporter GLUT4 expression, which is encoded by the SCL2A4 gene, and the related mechanisms. For this, 3T3-L1 adipocytes were incubated in the presence of a selective antagonist of CB1 receptor, AM251 (1-(2,4-Dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide). After 2, 4 or 24 h, cells were harvest to evaluate GLUT4 mRNA (real time PCR) and protein (western blotting), and NFkappaB activation specifically on the promoter of SLC2A4 gene (EMSA). Acute and chronic incubation for 4 or 24 h with AM 251 expressively increased GLUT4 protein content (P<0.001) but did not altered GLUT4 mRNA expression. Increased GLUT4 mRNA expression was only observed after 2 h of AM 251 treatment (P<0.001). Considering the participation of NF-kappaB in the SLC2A4 gene expression, AM251 was able to increase NF-kappaB activation in adipocytes only after 24 h incubation. In conclusion, the present data shows that the CB1 receptor inhibition markedly increases GLUT4 expression in adipocytes. Evidences point out to an important participation of the inflammatory transcriptional factor NFkappaB on the modulation of the SLC2A4 gene expression by CB1 receptor. FAPESP (08/09194-4 and 07/50554-1).