EFFECT OF ENDOTOXIN AND CYTOKINES ON LIPOPROTEIN-LIPASE ACTIVITY IN MICE

Endotoxin (lipopolysaccharide [LPS]) stimulates the production of cytokines, which mediate many of the metabolic effects associated with infection. In LPS-sensitive C57B1/6 mice, LPS doses as low as 0.01 mu g per mouse decreased adipose tissue lipoprotein lipase (LPL) activity by greater than 50%. In LPS-resistant C3H/HeJ mice, which do not produce cytokines in response to LPS, doses of LPS as high as 10 mu g per mouse did not affect LPL activity in adipose tissue. In muscle of C57B1/6 mice, LPL activity was decreased by 27% after 10 mu g of LPS, whereas in C3H/HeJ mice there was no effect. These results indicate that the LPS-induced decrease in both adipose and muscle LPL activity is mediated by cytokines. Tumor necrosis factor (TNF), interleukin (IL)-1, leukemia-inhibiting factor (LIF), interferon alfa, and interferon gamma all decreased adipose tissue LPL activity in intact mice. In Skeletal and cardiac muscle, only IL-l and interferon gamma decreased LPL activity, whereas TNF, LIF, and interferon alfa had no effect. Inhibition of TNF activity blocked the increase in serum triglycerides that is characteristically observed after LPS but did not affect the ability of LPS to decrease adipose tissue LPL activity. Inhibition of IL-1 activity with IL-1 receptor antagonist partially inhibited the increase in serum triglycerides; however, the ability of LPS to decrease LPL activity in either adipose or muscle tissue was not affected. These data indicate that although TNF and IL-1 play a role in mediating the increase in serum triglyceride levels, these cytokines do not play a crucial role in the inhibition of either adipose or muscle LPL activity. These results also indicate that the decrease in LPL activity is not a key event responsible for the increase in serum triglyceride levels. In conclusion, although the inhibition of LPL activity produced by LPS is mediated by cytokines, these effects are not dependent on either TNF or IL-1. Changes in LPL are not essential for the induction of hypertriglyceridemia but may influence the distribution of nutrients.