Transforming growth factor-beta enhances and pro-inflammatory cytokines inhibit OB gene expression in 3T3-L1 adipocytes

Leptin is a protein which is encoded by the obese (ob) gene. It is synthesized by adipocytes and binds to receptors in the hypothalamus, thereby suppressing appetite and increasing the metabolic rate. When mouse 3T3-L1 cells are induced to differentiate into adipocytes, they bean to constitutively express low levels of oh mRNA. Using reverse transcription and a semi-quantitative polymerase chain reaction, the experiments described herein demonstrate that the antiinflammatory cytokine transforming growth factor-p increases steady state ob mRNA. Conversely, treatment of 3T3-L1. adipocytes with the pro-inflammatory cytokines interleukin-1 beta, interleukin-6, interleukin-11, and tumor necrosis factor-alpha results in a decrease in ob transcripts. When considered in the context of animal studies showing that interleukin-1 and tumor necrosis factor-alpha induce leptin and ob mRNA, these results suggest that pro-inflammatory cytokines induce ob gene transcription in vivo via secondary mediators such as transforming growth factor-beta. (C) 1997 Academic Press.