Endotoxin-induced alteration in the expression of leptin and β3-adrenergic receptor in adipose tissue

Cytokines, such as tumor necrosis factor (TNF) and interleukin-g, may contribute to the anorexia and cachexia of infection, cancer, and AIDS. The present study tests the hypothesis that endotoxin alters the expression of two key fat cell proteins, leptin and beta(3)-adrenergic receptor (beta(3)-AR), through a mechanism involving TNF-alpha. Increasing doses of Escherichia coli endotoxin (lipopolysaccharide, LPS) resulted in dose-dependent elevations of plasma leptin (maximal response similar to 7-fold, half-maximal effective dose of similar to 16 mu g/100 g body wt) and white fat leptin mRNA in C3/HeOUJ mice. LPS also produced a large decrease in adipose tissue beta(3)-AR mRNA and a parallel reduction in beta-agonist-induced activation of adenylyl cyclase. Changes in plasma leptin and beta 3-AR mRNA mere preceded by an approximately threefold increase in white fat TNF mRNA. TNF administration resulted in changes similar to those seen with LPS. We conclude that endotoxemia results in an induction of leptin mRNA and a decrease in beta(3)-AR mRNA in adipose tissue, an effect that may be mediated by alterations in TNF-alpha.