CYTOKINES INDUCE CATABOLIC EFFECTS IN CULTURED ADIPOCYTES BY MULTIPLEMECHANISMS

Previous studies have demonstrated that some cytokines induce a coordi nate catabolic response in adipose cells which leads to decreased fat storage. The mechanisms by which cytokines cause these effects are unk nown. The primary purpose of the present study was to determine the ef fects of TNF, IL-1, IFN-alpha and IFN-alpha on the mRNA levels of the key enzymes involved in fat metabolism in 3T3-F442A adipocytes. TNF, I L-1, IFN-alpha and IFN-gamma decreased lipoprotein lipase activity and increased lipolysis in adipocytes. TNF, IFN-alpha and IFN-gamma decre ased fatty acid synthesis while IL-1 increased fatty acid synthesis. H owever, the cytokine effects on mRNA levels were not always consistent with the observed changes in activity and were unique for each cytoki ne. Specifically, while all cytokines decreased LPL activity, only TNF and IFN-gamma decreased LPL mRNA levels. In addition, while TNF, IFN- alpha and IFN-gamma decreased fatty acid synthesis, only TNF significa ntly decreased the mRNA levels of both acetyl CoA carboxylase and fatt y acid synthase, the key enzymes in fatty acid synthesis. IFN-alpha an d IFN-gamma decreased fatty acid synthase mRNA levels without signific antly altering acetyl CoA carboxylase mRNA. IL-1 caused a slight incre ase in fatty acid synthesis and increased acetyl CoA carboxylase mRNA levels. Finally, while all cytokines increased lipolysis, hormone sens itive lipase mRNA levels were decreased by TNF, IFN-alpha and IFN-gamm a treatment. These results indicate that the regulation of adipocyte l ipid metabolism by cytokines is complex and that coordinate changes in mRNA levels cannot account for the observed metabolic changes. Each c ytokine works via a different signalling pathway and induces specific patterns of metabolic alterations and mRNA regulation in 3T3-F442A adi pocytes.