Augmented Production of Tumor Necrosis Factor-α in Obese Mice

Abstract

Non-insulin-dependent diabetes mellitus develops in obesity. The insulin resistance of this disease may be mediated by tumor necrosis factor-α (TNF-α). In particular, the TNF-α derived from adipose tissues might be involved in the induction of peripheral insulin resistance in rodent models of obesity. In general, monocytes/macrophages have been considered as the major source of TNF-α. This study was designed to examine the potential production of TNF-α from monocyte/macrophages in obese mice. In obese ( ob/ob) and obese diabetic ( db/db) mice, both of which are known to have severe insulin resistance, unstimulated serum bioactivity of TNF-α was significantly higher than that in lean control mice. Spontaneous TNF-α mRNA expression in splenic macrophages was also enhanced in obese mice, but not in monosodium- l-glutamate (MSG)-induced obese mice which have no insulin resistance. In addition, both ob/ob and db/db mice produce more TNF-α than lean mice upon in vivo lipopolysaccharide (LPS) stimulation. The LPS-induced increase in serum TNF-α activity was not observed in MSG-induced obese mice. Taken together, it is postulated that TNF-α produced by monocytes/macrophages may also play an important role in the genesis of insulin resistance in obesity. Further study is needed to reveal the mechanism of enhanced TNF-α production in obese states and its possible etiologic relevance to obesity.