LEUKEMIA INHIBITORY FACTOR INDUCES CHANGES IN LIPID-METABOLISM IN CULTURED ADIPOCYTES

Cytokines induce a number of changes in lipid metabolism that can prod uce hyperlipidemia. Leukemia inhibitory factor (LIF), a recently disco vered cytokine, has been suggested to play a role in the cancer cachex ia syndrome through its ability to decrease lipoprotein lipase (LPL) a ctivity. This study explores the mechanism by which LIF decreases LPL activity in cultured adipocytes and determines its effects on fatty ac id synthesis and lipolysis to see if it shares the same catabolic effe cts on fat cells as seen with other cytokines, such as tumor necrosis factor (TNF). LIF decreased LPL activity in cultured adipocytes by 44% compared with an 85% decrease produced by TNF. Although the percent d ecrease in LPL activity is not as great in LIF-incubated adipocytes as in TNF-incubated adipocytes, the half-maximal doses for both cytokine s are similar. LPL messenger RNA levels paralleled LPL activity in the LIF-treated adipocytes, suggesting that the effect of LIF on LPL acti vity is predominantly mediated through transcriptional regulation. In contrast to TNF, LIF tended to increase the de novo synthesis of fatty acids. Acetyl coenzyme-A carboxylase messenger RNA levels paralleled the changes seen in fatty acid synthesis for both cytokines. LIF cause d a small increase in lipolysis, whereas TNF increased lipolysis by gr eater than 2-fold. These results demonstrate that the catabolic effect s of LIF are weaker than those of TNF and are predominantly directed t oward decreasing LPL activity, which may contribute to the hyperlipide mia associated with infection, inflammation, and cancer.