LIF AND CNTF, WHICH SHARE THE GP130 TRANSDUCTION SYSTEM, STIMULATE HEPATIC LIPID-METABOLISM IN RATS

We determined the effects of leukemia inhibitory factor (LIF) and cili ary neurotrophic factor (CNTF) on lipid metabolism in intact rats. Adm inistration of LIF and CNTF increased serum triglycerides in a dose-de pendent manner with peak values at 2 h. The effects of LIF and CNTF on serum cholesterol were very small, and serum glucose was unaffected. Both LIF and CNTF stimulated hepatic triglyceride secretion, hepatic d e novo fatty acid synthesis, and lipolysis. Pretreatment with phenylis opropyl adenosine, which inhibits lipolysis, partially inhibited LIF- and CNTF-induced hypertriglyceridemia. Interleukin-4, which inhibits c ytokine-induced hepatic fatty acid synthesis, also partially inhibited LIF- and CNTF-induced hypertriglyceridemia. These results indicate th at both lipolysis and de novo fatty acid synthesis play a role in prov iding fatty acids for the increase in hepatic triglyceride secretion. Neither indomethacin nor adrenergic receptor antagonists affected the hypertriglyceridemia. The combination of LIF plus CNTF showed no addit ive effects consistent with the action of both cytokines through the g p130 transduction system. Thus LIF and CNTF have similar effects on li pid metabolism; they join a growing list of cytokines that stimulate h epatic triglyceride secretion and may mediate the changes in lipid met abolism that accompany the acute phase response.