Cannabinoid Cb1 receptor-mediated effects on white and brown adipocytes

The endocannabinoid system has emerged as a critical component in the control of energy homeostasis. It stimulates a positive energy balance via both central and peripheral pathways and is considered a general stress-recovery system. Blockade of the endocannabinoid Cb1 receptor promotes weight loss in obese individuals. Cb1 receptors are expressed in adipocytes. However, direct Cb1 receptor-mediated action on major levels of adipocyte function have not been elucidated. Here, we demonstrate a direct role for cannabinoid signalling to control glucostatic adipokine expression and thermogenesis in white and brown adipocytes. Direct stimulation of differentiated white adipocytes with the Cb1 receptor agonist WIN 55212–2 (100nM) for 2h increased mRNA levels of the novel insulin-mimetic adipokine visfatin by 60% (p<0.05). In contrast, adiponectin mRNA levels were decreased by 30% relative to controls (p<0.05). In differentiated brown adipocytes, treatment with the selective Cb1 receptor agonist decreased protein expression of the thermogenic UCP-1 by 50% (p<0.01) in a dose-dependent manner. This effect was independent of an effect on adipocyte differentiation, since chronic stimulation of Cb1 receptor signalling did not affect cell morphology and lipid accumulation. Taken together, these data provide evidence for direct cannabinoid receptor-mediated effects on several levels of adipose function. These direct effects appear to favour energy storage and associated insulin resistance.