CYTOKINES INDUCE CATABOLIC EFFECTS IN CULTURED ADIPOCYTES BY MULTIPLE MECHANISMS

Previous studies have demonstrated that some cytokines induce a coordinate catabolic response in adipose cells which leads to decreased fat storage. The mechanisms by which cytokines cause these effects are unknown. The primary purpose of the present study was to determine the effects 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, IL-1, IFN-alpha and IFN-gamma decreased lipoprotein lipase activity and increased lipolysis in adipocytes. TNF, IFN-alpha and IFN-gamma decreased fatty acid synthesis while IL-1 increased fatty acid synthesis. However, the cytokine effects on mRNA levels were not always consistent with the observed changes in activity and were unique for each cytokine. 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 significantly decreased the mRNA levels of both acetyl CoA carboxylase and fatty acid synthase, the key enzymes in fatty acid synthesis. IFN-alpha and IFN-gamma decreased fatty acid synthase mRNA levels without significantly altering acetyl CoA carboxylase mRNA. IL-1 caused a slight increase in fatty acid synthesis and increased acetyl CoA carboxylase mRNA levels. Finally, while all cytokines increased lipolysis, hormone sensitive lipase mRNA levels were decreased by TNF, IFN-alpha and IFN-gamma treatment. These results indicate that the regulation of adipocyte lipid metabolism by cytokines is complex and that coordinate changes in mRNA levels cannot account for the observed metabolic changes. Each cytokine works via a different signalling pathway and induces specific patterns of metabolic alterations and mRNA regulation in 3T3-F442A adipocytes.