This observations bringing into contrast the roles of the two major proinflammatory cytokines as circulating or local signals. TNF-alpha not released to the systemic circulation, so the any effect must be from signaling to the same adipocite. IL-6 is released in substantial amounts into the systemic circulations that for may signal to distant tissues in particular the liver and perhaps to skeletal muscles or other adipose tissues. TNF-alpha may play a role in systemic insulin resistance only if the local effects of TNF-alpha included modulation of fatty acids and some other mechanisms.