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A PPAR agonist improves TNF-α-induced insulin resistance of adipose tissue in mice

2003; Elsevier BV; Volume: 309; Issue: 2 Linguagem: Inglês

10.1016/j.bbrc.2003.07.007

1090-2104

Manabu Shibasaki, Kazuo Takahashi, T. Itou, Hideaki Bujo, Yoshiro Saito,

Adipokines, Inflammation, and Metabolic Diseases

Thiazolidinediones (TZDs), agonists for PPARs, have been shown to block the inhibitory effects of TNF-α on insulin action using cultured cells. In order to clarify the in vivo effects of TZDs on the inhibition of insulin sensitivity by TNF-α, insulin action in muscles and adipose tissues was assessed in the TNF-α-overexpression mice model using transplantation of cells secreting the TNF-α protein. After the pioglitazone treatment for 4 weeks, glucose uptake, insulin-induced IRS-1 phosphorylation, and lipoprotein lipase mRNA levels were analyzed. Pioglitazone did not ameliorate TNF-α-induced hyperinsulinemia in this model, as assessed by the OGTT. Glucose uptake and lipoprotein lipase mRNA levels were decreased by TNF-α in adipose tissues from the TNF-α-overexpressing mice, and pioglitazone blocked these inhibitions by TNF-α. On the other hand, in muscles, pioglitazone did not reverse the effects of TNF-α on insulin-induced phosphorylation of IRS-1, glucose uptake, and lipoprotein lipase mRNA levels. Present study revealed the different sensitivities of pioglitazone for the recovery of decreased insulin action in a TNF-α-overexpressing model using cell transplantation. These results suggest that the effect of TZDs is dependent on the fat distribution and accumulation in humans.