Augmented production of tumor necrosis factor-alpha in obese mice.
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.
Yamakawa
T
T
Third Department of Internal Medicine, Yokohama City University School of Medicine, Japan.
Tanaka
S
S
Yamakawa
Y
Y
Kiuchi
Y
Y
Isoda
F
F
Kawamoto
S
S
Okuda
K
K
Sekihara
H
H
D000818:Animals; D015152:Blotting, Northern; D004797:Enzyme-Linked Immunosorbent Assay; D007333:Insulin Resistance / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000737:chemistry / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese / Q000378:metabolism*; D009000:Monocytes / Q000737:chemistry / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D013154:Spleen / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha