Endotoxin induced transcriptional regulation of leptin and beta-3 adrenergic receptor (b3AR) in mouse adipose tissue

Anorexia and cachexia, syndromes of progressive weight loss and wasting, frequently accompany many clinical settings including cancer, AIDS, infection, and other critical illness. Because of the importance of leptin (a novel peptide hormone released by fat cells which regulates appetite and metabolism), and b3AR (a novel metabolic beta receptor important in lipolysis and thermogenesis] in metabolic regulation, we hypothesized that tumor necrosis factor-alpha (TNFα) and other cytokines induced during the inflammatory response result in the transcriptional regulation of leptin and the b3AR. The present study examines the effects of endotoxin, a potent stimulator of cytokine production, on the adipocyte expression of TNFα, leptin and b3AR. (using RT-PCR and RNase, protection assays). Endotxin-sensitive C57BL/SNJ mice (n=5) received either saline or E. Coli endotoxin 500ug/100g IP. Pat samples, obtained after treatment and an overnight fast (16 h). demonstrated increased TNFα and leptin mRNA (>3-fold) and reduced b3AR mRNA in animals receiving endotoxin. These data suggest that endotoxin may affect metabolism and appetite via transcriptional changes in leptin synthesis, while alterations in TNFα and b3AR expression may contribute to the insulin resistance of sepsis syndromes.