Tumor necrosis factor (TNF)-alpha induces leptin production through the p55 TNF receptor

Tumor necrosis factor (TNF)-alpha acts directly on adipocytes to increase p roduction of the lipostatic factor, leptin. However, which TNF receptor (TN FR) mediates this response is not known. To answer this question, leptin wa s measured in plasma of wild-type (WT) p55, and p75 TNFR knockout (KO) mice injected intraperitoneally with murine TNF-alpha and in supernatants from cultured WT, p55, and p75 TNFR KO adipocytes incubated with TNF-alpha. Lept in also was measured in supernatants from C3H/HeOuJ mouse adipocytes cultur ed with blocking antibodies to each TNFR and TNF-alpha as well as in supern atants from adipocytes incubated with either human or murine TNF-alpha, whi ch activate either one or both TNFR, respectively. The results using all fo ur strategies show that the induction of leptin production by TNF-alpha req uires activation of the p55 TNFR and that although activation of the p75 TN FR alone cannot cause leptin production, its presence affects the capabilit y of TNF-alpha to induce leptin production through the p55 TNFR. These resu lts provide new information on the interplay between cells of the immune sy stem and adipocytes.