Adiponectin expression is induced by vitamin E via a peroxisome proliferator-activated receptor gamma-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 (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.
Landrier
Jean-François
JF
Unité Mixte de Recherche, Faculté de Médecine, 1260 Institut National de la Recherche Agronomique, Marseille, France. jf.landrier@univmed.fr
Gouranton
Erwan
E
El Yazidi
Claire
C
Malezet
Christiane
C
Balaguer
Patrick
P
Borel
Patrick
P
Amiot
Marie-Josèphe
MJ
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D052242:Adiponectin / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D014810:Vitamin E / Q000008:administration & dosage / Q000494:pharmacology*; D014815:Vitamins / Q000008:administration & dosage / Q000494:pharmacology
C097240:15-deoxy-delta(12,14)-prostaglandin J2; C457499:2-chloro-5-nitrobenzanilide; D052242:Adiponectin; D000813:Anilides; D047495:PPAR gamma; D011993:Recombinant Fusion Proteins; D014815:Vitamins; D014810:Vitamin E; D008156:Luciferases; D015230:Prostaglandin D2