Autocrine Inhibition of Leptin Production by Tumor Necrosis Factor-α (TNF-α) through TNF-α Type-I Receptorin Vitro

Abstract

The aim of this study was to find factors which regulate m-leptin secretion during pregnancy. Mouse parametrial adipocytes from day 13 of pregnancy were cultured with or without mouse placental lactogen (mPL)-I, mPL-II, or mouse tumor necrosis factor-α (mTNF-α) and mouse-leptin (m-leptin) concentration in the medium was assessed by RIA. Up to four days of mPL-I or mPL-II treatment did not affect m-leptin secretion. However, mTNF-α, which is produced by adipocytes, significantly inhibited m-leptin secretion in a dose- and time-dependent manner. Antibody to mTNF-α completely blocked the inhibitory effect of mTNF-α on m-leptin secretion. mTNF-α significantly inhibited the expression of m-leptin messenger RNA. Agonistic polyclonal antibody directed against the mTNF-type-I receptor (mTNF-RI) significantly inhibited m-leptin secretion, but the anti-mTNF-RII antibody did not change m-leptin secretion. Moreover, human TNF-α (h-TNF-α) also inhibited human-leptin (h-leptin) secretion by cultured human adipocytes collected from the subcutaneous fat of pregnant women. These results suggest that TNF-α, which is secreted by adipocytes, inhibits m-leptin secretion through mTNF-RI and suggest the presence of an autocrine or paracrine regulation of leptin secretion in human and mouse adipose tissuein vivo.