Objective:

In order to characterize the regulation of resistin gene expression, we explore the effect of tumornecrosis factor- (TNF-) on resistin mRNA expression and its underlying mechanism in 3T3-L1 adipocytes.

Methods and Procedures:

Differentiated 3T3-L1 adipocytes were treated for 24 h with 0–10 ng/ml of TNF- or with 2.5 ng/ml of TNF- for 0–24 h, and then resistin mRNA levels were measured by northern blotting. To further explore the involvement of nitric oxide (NO) in TNF-–regulated resistin expression, the effect of the NO donor, sodium nitroprusside (SNP), on resistin mRNA levels in adipocytes and the effect of the nitric oxide synthase (NOS) inhibitors, N^G-nitro-L-arginine methyl ester (L-NAME), and S,S'-1,3-phenylene-bis(1,2-ethanediyl)-bis-isothiourea2HBr (PBITU), on the TNF- effect in adipocytes were examined. The effects of TNF- on inducible NOS (iNOS) protein expression in adipocytes were also measured by western blotting.

Results:

Our results showed that TNF- caused a dose-dependent reduction in resistin mRNA levels. This effect seemed to be associated with the TNF-–induced expression of iNOS. The results showed that TNF- induced iNOS expression and release of NO after 24-h treatment of differentiated 3T3-L1 adipocytes. Pretreatment with L-NAME and PBITU significantly reversed the TNF-–induced downregulation of resistin expression, while treatment with SNP mimicked the inhibitory effect of TNF- on resistin expression. In addition, pretreatment with protein tyrosine kinase (PTK) inhibitors, genistein and AG-1288, prevented TNF-–induced iNOS expression and subsequent resistin downregulation.

Discussion:

Our data suggest that TNF- suppresses resistin expression by inducing iNOS expression, thus causing overproduction of NO, which downregulates resistin gene expression.

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