IDENTIFICATION OF MACROPHAGE-MIGRATION INHIBITORY FACTOR IN ADIPOSE-TISSUE AND ITS INDUCTION BY TUMOR-NECROSIS-FACTOR-ALPHA

Macrophage migration inhibitory factor (MIF) has been rediscovered as a proinflammatory cytokine, pituitary hormone, and glucocorticoid-indu ced immunoregulator. A survey of tissue distribution revealed that MIF expression is not limited to T lymphocytes, but exists in several oth er tissues; however, its presence in adipose tissue has never been inv estigated. In this study, we examined the expression of MIF in adipose tissue using the rat epididymal fat pad and murine 3T3-L1 adipocytes. Northern and Western blot analyses revealed the expression of MIF mRN A and MIF protein, respectively, in both the fat pad and the adipocyte cell line. In immunohistochemistry, a positive staining reaction with an anti-rat MIF antibody was detected largely in the cytosol of adipo cytes of the epididymal fat pad. To examine the production and release of MIF by adipocytes, we examined its content in the culture medium o f the 3T3-L1 adipocytes. The results showed that MIF content was 1.6 /- 0.48 ng/ml (mean +/- SD) after 24 hr culture, and the content was i ncreased up to 9.7 +/- 2.8 ng/ml by stimulation with TNF-alpha (50 nM) . Since TNF-alpha produced in adipocytes is known to induce insulin re sistance, the results suggest the possibility that MIF plays an import ant role in the mechanism of insulin resistance often observed in obes ity and diabetes via regulation of TNF-alpha expression. (C) 1997 Acad emic Press.