Adiponectin Expression Is Induced by Vitamin E via a Peroxisome Proliferator-Activated Receptor γ-Dependent Mechanism

Adiponectin is a well-known adipokine secreted by adipocytes that presents insulin-sensitizing properties. The regulation of expression of this adipokine by micronutrients is largely unknown. We demonstrate here that adiponectin expression is induced in adipocytes after exposure to tocopherols via the peroxisome proliferator-activated receptor gamma (PPAR gamma) pathway. Vitamin E force feeding resulted in an induction of adiponectin in mice at both mRNA and protein levels. Adiponectin mRNA and protein secretion were also increased by vitamin E (alpha- and gamma-tocopherol) in 3T3-L1 cells, together with PPAR gamma mRNA, independent of an antioxidant effect. In transient transfections, both alpha- and gamma-vitamers induced the luciferase gene reporter under the control of a human adiponectin promoter via a PPAR-responsive element. The induction of adiponectin by tocopherols seems to be PPAR gamma dependent, because it was blocked by the specific antagonist GW9662. Finally, we showed that intracellular concentrations of a PPAR gamma endogenous ligand, 15-deoxy-Delta 12,14-prostaglandin J2, increased after treatment with tocopherols in 3T3-L1 cells. In summary, vitamin E up-regulates adiponectin expression via a mechanism that implicates PPAR gamma together with its endogenous ligand 15-deoxy-Delta 12,14-prostaglandin J2. The induction of adiponectin via an original molecular mechanism could be considered as the basis for the beneficial effect of vitamin E on insulin sensitivity. (Endocrinology 150: 5318-5325, 2009)