Decreased expression of murine PPARgamma 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 PPARgamma. PPARgamma 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 PPARgamma expression. In these studies, we examined the effect of endotoxin or its proximal mediator, tumor necrosis factor (TNF), on the expression of PPARgamma in white (WAT) and brown adipose tissue (BAT) in CD-1 mice. We report that treatment with endotoxin, but not TNF, transiently decreased PPARgamma mRNA levels 4 hr after treatment. However, endotoxin or TNF treatment decreased PPARgamma protein levels after 18 hr, which was at a time when LPL mRNA levels were also depressed. These data suggest that decreased PPARgamma expression following endotoxin or TNF treatment may contribute to the hyperlipidemia due to decreased expression of LPL, which would impair triglyceride clearance.