Synergistic effects of ascorbic acid and thiazolidinedione on secretion of high molecular weight adiponectin from human adipocytes

Aim: To test the hypothesis that ascorbic acid (AA) and thiazolidinedione (TZD) would have additive effects on HMW adiponectin secretion by virtue of different modes of action. Methods: We determined the effects of supplementation of AA and/or TZD on expression and secretion of total and HMW adiponectin from human Simpson–Golabi–Behmel syndrome (SGBS) adipocytes in the absence or presence of the proinflammatory cytokine TNFα. Results: AA supplementation significantly increased secretion of HMW adiponectin (1.7‐fold) without altering adiponectin expression or total adiponectin secretion. TZD significantly increased expression (3‐fold) and secretion of total (1.4‐fold) but not HMW adiponectin. Combined supplementation resulted in a significant increase in expression (3‐fold) and secretion of total (1.8‐fold) and HMW (5‐fold) adiponectin. Similar results were seen in cells co‐treated with TNFα. Conclusions: These data show that AA and TZD have synergistic rather than simple additive effects on secretion of HMW adiponectin from human adipocytes and raise the possibility that differences in AA levels may contribute to the variability in adiponectin multimer profiles and efficacy of TZD in humans. Our results also provide a rationale for longitudinal clinical trials investigating the effects of AA supplementation with or without TZD on adiponectin and metabolic profiles.