The endocannabinoid system has recently emerged as an important modulator of several functions of adipose tissue by altering cell proliferation and gene expression. In this work, we investigated the effects of CB1 activation/blockade in mouse 3T3-L1 adypocite cells by using WIN55,212, a CB1/CB2 agonist and rimonabant, a specific CB1 antagonist, in different experimental settings such as acute treatment on pre-adipocytes and on mature adipocytes, and chronic treatment during differentiation process. The gene expression was first analyzed by semi-quantitative RT-PCR and then confirmed by Real-TIME PCR for selected genes. We found that CB1 and FAAH mRNAs were both up-regulated by WIN55,212 and down regulated by SR141716, this effect was stronger in pre-adipocytes than in mature adipocytes. Furthermore, in pre-adipocytes, rimonabant was able to down-regulate PPAR-γ expression, whereas WIN55,212 gave an opposite effect. Moreover, rimonabant was also able to stimulate UCP1 and UCP2 mRNA expression.
Among adipokynes, adiponectin mRNA has been shown to be down-regulated by WIN55,212 and up-regulated by rimonabant, whereas visfatin, apelin and IL-6 mRNAs resulted up-regulated by WIN55,212 and down regulated by rimonabant. In the same cells, rimonabant reduced lipogenic gene expression, in particular of FAS, ACC, LPL, SCD-1, DGAT-2 mRNAs, whereas WIN55,212 up-regulated these genes suggesting a stimulatory role of endocannabinoids on fatty acids and triglycerides biosynthesis.
All together, these results indicate that endocannabinoid system is able to stimulate differentiation of pre-adipocytes towards adipocytes and to directly influence several metabolic processes of these cells including their secretory profile.