DECREASED EXPRESSION OF MURINE PPAR-GAMMA IN ADIPOSE-TISSUE DURING ENDOTOXEMIA

Infection-induced hyperlipidemia develops due to a combination of fact ors, one of which is decreased clearance of lipids from the bloodstrea m due to depressed synthesis of lipoprotein lipase (LPL). Recently, th e peroxisome proliferator activated receptors (PPARs) have been shown to be important in the regulation of LPL, particularly PPAR gamma. PPA R gamma and its heterodimerization partner, RXR alpha have been shown to be transcriptional activators of LPL in co-transfection analysis. T herefore, we hypothesized that the decrease in LPL expression during e ndotoxemia may be a result of depressed PPAR gamma expression. In thes e studies, we examined the effect of endotoxin or its proximal mediato r, tumor necrosis factor (TNF), on the expression of PPAR gamma in whi te (WAT) and brown adipose tissue (BAT) in CD-1 mice. We report that t reatment with endotoxin, but not TNF, transiently decreased PPAR gamma mRNA levels 4 hr after treatment. However, endotoxin or TNF treatment decreased PPAR gamma protein levels after 18 hr, which was at a time when LPL mRNA levels were also depressed. These data suggest that decr eased PPAR gamma expression following endotoxin or TNF treatment may c ontribute to the hyperlipidemia due to decreased expression of LPL, wh ich would impair triglyceride clearance.