PPARß/d ameliorates fructose-induced insulin resistance in adipocytes by preventing Nrf2 activation.
Por:
Barroso E, Rodríguez-Rodríguez R, Chacón MR, Maymó-Masip E, Ferrer L, Salvadó L, Salmerón E, Wabistch M, Palomer FX, Vendrell J, Wahli W and Vazquez M
Publicada:
1 may 2015
Resumen:
We studied whether PPARß/d deficiency modifies the effects of high fructose intake (30% fructose in drinking water) on glucose tolerance and adipose tissue dysfunction, focusing on the CD36-dependent pathway that enhances adipose tissue inflammation and impairs insulin signaling. Fructose intake for 8 weeks significantly increased body and liver weight, and hepatic triglyceride accumulation in PPARß/d-deficient mice but not in wild-type mice. Feeding PPARß/d-deficient mice with fructose exacerbated glucose intolerance and led to macrophage infiltration, inflammation, enhanced mRNA and protein levels of CD36, and activation of the JNK pathway in white adipose tissue compared to those of water-fed PPARß/d-deficient mice. Cultured adipocytes exposed to fructose also exhibited increased CD36 protein levels and this increase was prevented by the PPARß/d activator GW501516. Interestingly, the levels of the nuclear factor E2-related factor 2 (Nrf2), a transcription factor reported to up-regulate Cd36 expression and to impair insulin signaling, were increased in fructose-exposed adipocytes whereas co-incubation with GW501516 abolished this increase. In agreement with Nrf2 playing a role in the fructose-induced CD36 protein level increases, the Nrf2 inhibitor trigonelline prevented the increase and the reduction in insulin-stimulated AKT phosphorylation caused by fructose in adipocytes. Protein levels of the well-known Nrf2 target gene
Open Access
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