Decreased expression of murine PPAR gamma in adipose tissue during endotoxemia

Infection-induced hyperlipidemia develops due to a combination of factors, one of which is decreased clearance of lipids from the bloodstream due to depressed synthesis of lipoprotein lipase (LPL). Recently, the peroxisome proliferator activated receptors (PPARs) have been shown to be important in the regulation of LPL, particularly PPAR gamma. PPAR gamma and its heterodimerization partner, RXR alpha have been shown to be transcriptional activators of LPL in co-transfection analysis. Therefore, we hypothesized that the decrease in LPL expression during endotoxemia may be a result of depressed PPAR gamma expression. In these studies, we examined the effect of endotoxin or its proximal mediator, tumor necrosis factor (TNF), on the expression of PPAR gamma in white (WAT) and brown adipose tissue (BAT) in CD-1 mice. We report that treatment 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 decreased PPAR gamma expression following endotoxin or TNF treatment may contribute to the hyperlipidemia due to decreased expression of LPL, which would impair triglyceride clearance.