Obesity is commonly associated with development of insulin resistance and 
systemic evidence of inflammation. Macrophages contribute to inflammatory 
amplification in obesity and may contribute directly to insulin resistance and 
the development of nonalcoholic fatty liver disease through the production of 
inflammatory cytokines, including tumor necrosis factor (TNF)-alpha. To test 
this hypothesis, we transplanted male wild-type (WT) and TNF-alpha deficient 
(KO) mice with either TNF-alpha-sufficient (TNF-alpha(+/+)) or 
TNF-alpha-deficient (TNF-alpha(-/-)) bone marrow. After consuming a high-fat 
diet for 26 wk, metabolic and morphometric characteristics of the animals were 
analyzed. While there were no differences in terms of relative weight gain, body 
composition analysis yielded a lower relative adipose and higher relative lean 
mass in mice lacking TNF-alpha, which was partially explained by reduced 
epididymal fat pad and liver weight. TNF-alpha(-/-) -->KO mice exhibited 
enhanced insulin sensitivity compared with that observed in TNF-alpha(+/+)-->KO 
mice; remarkably, no protection against insulin resistance was provided by 
transplanting TNF-alpha(-/-) bone marrow in WT mice compared with 
TNF-alpha(+/+)-->WT. The preserved insulin sensitivity seen in 
TNF-alpha(-/-)-->KO mice provided protection against the development of hepatic 
steatosis. Taken together, these data indicate that macrophage-derived TNF-alpha 
contributes to the pattern and extent of fat accumulation and insulin resistance 
in diet-induced obesity; however, this contribution is negligible in the 
presence of host-derived TNF-alpha.