Endocannabinoids in adipocytes during differentiation and their role in glucose uptake

The molecular basis for the control of energy balance by the endocannabinoidanandamide (AEA) is still unclear. Here, we show that murine 3T3-L1 fibroblastshave the machinery to bind, synthesize and degrade AEA, and that theirdifferentiation into adipocytes increases by approximately twofold the bindingefficiency of cannabinoid receptors (CBR), and by approximately twofold andapproximately threefold, respectively, the catalytic efficiency of the AEAtransporter and AEA hydrolase. In contrast, the activity of the AEA synthetaseand the binding efficiency of vanilloid receptor were not affected by thedifferentiation process. In addition, we demonstrate that AEA increases byapproximately twofold insulin-stimulated glucose uptake in differentiatedadipocytes, according to a CB1R-dependent mechanism that involves nitric oxidesynthase, but not lipoxygenase or cyclooxygenase. We also show that AEA bindingto peroxisome proliferator-activated receptor-gamma, known to inducedifferentiation of 3T3-L1 fibroblasts into adipocytes, is not involved in thestimulation of glucose uptake.[...]