Augmented production of tumor necrosis factor-alpha in obese mice

Clin Immunol Immunopathol. 1995 Apr;75(1):51-6. doi: 10.1006/clin.1995.1052.


Non-insulin-dependent diabetes mellitus develops in obesity. The insulin resistance of this disease may be mediated by tumor necrosis factor-alpha (TNF-alpha). In particular, the TNF-alpha 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-alpha. This study was designed to examine the potential production of TNF-alpha 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-alpha was significantly higher than that in lean control mice. Spontaneous TNF-alpha mRNA expression in splenic macrophages was also enhanced in obese mice, but not in monosodium-L-glutamate (MST)-induced obese mice which have no insulin resistance. In addition, both ob/ob and db/db mice produce more TNF-alpha than lean mice upon in vivo lipopolysaccharide (LPS) stimulation. The LPS-induced increase in serum TNF-alpha activity was not observed in MSG-induced obese mice. Taken together, it is postulated that TNF-alpha 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-alpha production in obese states and its possible etiologic relevance to obesity.

MeSH terms

  • Animals
  • Blotting, Northern
  • Enzyme-Linked Immunosorbent Assay
  • Insulin Resistance / physiology
  • Lipopolysaccharides / pharmacology
  • Macrophages / chemistry
  • Macrophages / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese / metabolism*
  • Monocytes / chemistry
  • Monocytes / physiology
  • RNA, Messenger / analysis
  • Spleen / cytology
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / biosynthesis*
  • Tumor Necrosis Factor-alpha / genetics


  • Lipopolysaccharides
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha