KERATINOCYTE GROWTH-FACTOR INCREASES FATTY-ACID MOBILIZATION AND HEPATIC TRIGLYCERIDE SECRETION IN RATS

Keratinocyte growth factor (KGF) is a member of the fibroblast growth factor family that was originally identified as a keratinocyte mitogen after isolation from a lung fibroblast cell line. In this study, we d emonstrate that administration of KGF to mice and rats elevates serum lipid levels. In rats, 1 h after KGF administration, serum triglycerid e and FFA levels were increased with peak values at 2 h (1.9-fold incr ease). The increase in serum triglyceride levels was sustained for at least 16 h. Serum cholesterol levels were also increased, but the effe ct was delayed beginning at 4 h, with peak values at 16 h (1.27-fold i ncrease). KGF did not decrease the clearance of triglyceride-rich lipo proteins, but,increased hepatic triglyceride secretion. KGF stimulated lipolysis, but not hepatic de novo fatty acid synthesis, and the incr eased delivery of FFA to the liver plays a crucial role in the KGF-ind uced hypertriglyceridemia. Neither alpha- nor beta-adrenergic receptor antagonists affected the hypertriglyceridemia induced by KGF, indicat ing that endogenous catecholamines are not involved in mediating KGF-i nduced hypertriglyceridemia. These results demonstrate that KGF induce s hypertriglyceridemia by increasing hepatic triglyceride secretion, w ith the fatty acids provided lipolysis making a major contribution. Th us, KGF could modulate lipid metabolism in vivo.