Mulberry leaf extract increases adiponectin in murine 3T3-L1 adipocytes.

We have previously shown that mulberry leaf extract (MA) causes blood glucose levels to decrease in rats with streptozotocin-induced diabetes while enhancing glucose uptake by isolated fat cells. We hypothesized that the antidiabetic activity of MA is mediated via enhancement of adiponectin secretion and adipogenesis, which consequently decreases blood glucose. In the present study, we aimed to elucidate the molecular basis for the observed antidiabetic activity using murine 3T3-L1 preadipocyte cultures. We found that treatment of differentiating 3T3-L1 cells with MA at concentrations of 5, 15, and 45 μg/mL increased expression of adiponectin messenger RNA from 1.4-fold (control) to 1.5-, 1.95-, and 2.2-fold above basal values, respectively, while causing adiponectin secretion to increase from 70 ± 7.4 ng/mL to 100 ± 1.4, 138 ± 2.0, and 176 ± 21.4 ng/mL, respectively. Furthermore, we observed an increase in both lipid accumulation and messenger RNA expression of transcription factors, such as CCAAT/enhancer-binding protein α and peroxisome proliferator-activated receptor γ; and of the fatty acid-binding protein aP2 in differentiated 3T3-L1 cells pretreated with MA. Our findings indicate that the stimulatory effects of mulberry leaf extract on adipocyte proliferation and differentiation likely occur through up-regulation of adipogenic transcription factors and downstream gene expression. Such effects of mulberry leaf extract on adiponectin secretion and adipocyte activity may account for, at least in part, the antidiabetic effects of consumption of beverages containing mulberry leaves.