TNF-α Inhibits Insulin Action in Liver and Adipose Tissue: A Model of Metabolic Syndrome

Abstract

Several studies suggest that TNF-α contributes to the development of insulin resistance (IR). We compared transcriptional profiles of rat H-411E liver cells exposed to insulin in the absence or presence of TNF-α. We identified 33 genes whose expression was altered by insulin, and then reversed by TNF-α. Twenty-six of these 33 genes created a single network centered around: insulin, TNF-α, p38-MAPK, TGFb1; SMAD and STAT1; and enzymes and cytokines involved in apoptosis (CASP3, GADD45B, IL2, TNF-α, etc.). We analyzed our data together with other data of gene expression in adipocytes and found a number of processes common to both, for example, cell death and inflammation; intercellular signaling and metabolism; G-Protein, IL-10 and PTEN signaling. Moreover, the two datasets combined generated a single molecular network that further identified PTEN (a phosphatase) as a unique new link between insulin signaling, IR, and apoptosis reflecting the pathophysiology of “metabolic syndrome”.

metabolic syndrome model - liver cells - tissue culture - genomics - insulin - receptor and signaling - phosphorylation - energy utilization - apoptosis

References

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