ADIPOSE TISSUE-DERIVED TUMOR-NECROSIS-FACTOR-ALPHA ACTIVITY IS ELEVATED IN OLDER RATS

High levels of adipose tissue-derived tumor necrosis factor-alpha (AT- TNF) mRNA and protein have previously been associated with generic mod els of obesity and insulin resistance. Because there are endogenous TN F inhibitors it is unknown if AT-TNF activity is also increased. We hy pothesized that AT-TNF activity would increase in older ani mars becau se of an accumulation of fat mass. We chose to study 2 different-aged male Fischer 344 rate, 3-month-old (young) and 14-month-old (mature) b ecause fat mass should be quite different but insulin action on glucos e metabolism similar. Indeed, mature rats had over 1.5-fold more fat m ass, but whole body insulin resistance, as estimated by fasting plasma insulin, was similar to young rats. Mature rats had twice as much AT- TNF activity as the young in both the epididymal (EPI) and retroperito neal (Retro) fat pads (p <.0005). AT-TNF correlated with fasting plasm a insulin in Retro only fr = .48, p = .04). AT-TNF activity strongly c orrelated with cell size in both EPI and Retro (r = .79 and .81, respe ctively, p <.0001). Because cytokines can be regulated at several leve ls, AT-TNF activity, protein, and mRNA were measured AT-TNF protein le vels were higher in young rats, suggesting that these animals may secr ete an inhibitor that reduces AT-TNF activity. There were no significa nt differences in AT-TNF mRNA between groups. Since TNF has been shown to affect several key genes in tissue culture, mRNA for lipoprotein l ipase, hormone-sensitive lipase, and Glut4 were measured. No differenc e were found between groups. In summary AT-TNF activity increased in m ature animals in relation to adipose cell size.