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

Abstract

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 (PPARgamma) 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 PPARgamma 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 PPARgamma dependent, because it was blocked by the specific antagonist GW9662. Finally, we showed that intracellular concentrations of a PPARgamma endogenous ligand, 15-deoxy-Delta12,14-prostaglandin J2, increased after treatment with tocopherols in 3T3-L1 cells. In summary, vitamin E up-regulates adiponectin expression via a mechanism that implicates PPARgamma together with its endogenous ligand 15-deoxy-Delta12,14-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.

Vitamine E et physiologie du tissu adipeux

“…L'a-tocopherol est egalement capable de moduler les niveaux d'activation des facteurs de transcription comme le nuclear factor kB (NF-kB) et l'activator protein-1 (AP-1) (MaggiCapeyron et al, 2001). Nous avons montre que la vitamine E est capable de reguler l'expression de genes dont l'expression est dependante du recepteur nucleaire peroxisome proliferator activated protein g (PPARg ; (Landrier et al, 2009)) et que l'a-tocopherol module la synthese endogene de cholesterol et d'oxysterols en modulant probablement le clivage des sterol response element binding proteins (SREBPs ; (Landrier et al, 2010)). Ces regulations geniques expliqueraient en grande partie les nombreux effets non antioxydants de la vitamine E. Il est important de souligner que les mecanismes moleculaires ne sont pas specifiques a la vitamine E, celle-ci utilise des voies de signalisations communes a de nombreux autres modulateurs de l'expression genique.…”

“…L'induction de cette derniere, mise en evidence chez des souris gavees avec du g-tocopherol, a ete confirmee in vitro sur modele cellulaire adipocytaire 3T3-L1 avec le g-tocopherol mais aussi l'a-tocopherol, independamment de leur fonction antioxydante (Landrier et al, 2009). Compte-tenu du rôle cle de PPARg dans la regulation de l'adiponectine, nous nous sommes interesses a l'implication de ce recepteur nucleaire dans cette regulation, en utilisant un antagoniste specifique de PPARg abolissant l'induction de l'adiponectine par les tocopherols.…”

Impact of anti-inflammatory nutrients on obesity-associated metabolic-inflammation from childhood through to adulthood

“…1 (68)(69)(70) . Epigallocatechin gallate, lycopene and vitamin C impede NF-κB signalling, by targeting IKK and attenuate phosphorylation of extracellular signal related kinase, p-38 and JNK (67)(68)(69)71) . α-Tocopherol, in conjunction with vitamin D 3 ameliorates IL-6 production as well as increasing mRNA and protein expression of adiponectin in 3T3-L1 adipocytes (71,72) .…”

“…Epigallocatechin gallate, lycopene and vitamin C impede NF-κB signalling, by targeting IKK and attenuate phosphorylation of extracellular signal related kinase, p-38 and JNK (67)(68)(69)71) . α-Tocopherol, in conjunction with vitamin D 3 ameliorates IL-6 production as well as increasing mRNA and protein expression of adiponectin in 3T3-L1 adipocytes (71,72) . Moreover, Yang et al proposed that epigallocatechin gallate may improve insulin sensitivity in AT through reactive oxygen species scavenging functions, thus improving insulinstimulated glucose-uptake (70) .…”

The genomics of micronutrient requirements

“…Obese individuals have also been shown to have a lower level of the antioxidant vitamins C and E (Aasheim et al 2008). An adequate vitamin C level may contribute to maintenance of body weight, while vitamin E has been shown to impact adipocyte biology, leading to modulation of the secretion of adipokines (Landrier et al 2009;Amara et al 2014). However, the causality between low vitamin status and obesity remains difficult to be established, especially in humans.…”