Effect of leukemia inhibitory factor on feed intake and body temperature in sheep

Leukemia inhibitory factor (LIF) has been suggested to function as a potent inhibitor of feed intake in rodents. These studies were designed to determine whether LIF was found in the ovine hypothalamus and whether LIF inhibited feed intake in sheep. Sheep hypothalami were used to clone LIF to indicate presence of the gene in the hypothalamus. The sequence was similar to published data. Another group of sheep were provided intraventricular (ICV) cannulas and injected with doses of LIF at 250, 500, 1000 and 2500 ng per sheep, ICV. Feed intake was inhibited by the 1000 and 2500 ng dose (trt, P<0.0001; time X trt, P<0.02). All doses of LIF elevated temperature above 40 C, indicating a fever. In a second experiment, the sheep were injected ICV with 2500 ng LIF, and blood samples collected at 10 min intervals for 6 h for assay of luteinizing hormone (LH), growth hormone (GH) and 30 min interval samples assayed for glucose and free fatty acids.There was no effect of LIF on GH. There was no effect of trt for LH, but there was a timeXtrt interaction indicating reduced LH (P<0.0001). There was an effect of trt and timeXtrt interaction indicating elevated plasma free fatty acids (P<0.03; 0.001) and glucose (P<0.006; 0.0001). The effects of LIF on feed intake and other parameters is similar to the effects of LPS and leads to a hypothesis that LIF expression in response to LPS may be a component of the mechanism for feed intake inhibition in disease. While the effects of LIF to increase glucose and free fatty acids are similar to those seen with LPS in sheep, they are opposite to the effects of LIF in rodent models.