Nonogaki K, Pan X M, Moser A H, Staprans I, Feingold K R, Grunfeld C
Department of Medicine, University of California, San Francisco 94143, USA.
Endocrinology. 1995 Oct;136(10):4278-84. doi: 10.1210/endo.136.10.7664645.
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 demonstrate that administration of KGF to mice and rats elevates serum lipid levels. In rats, 1 h after KGF administration, serum triglyceride and FFA levels were increased, with peak values at 2 h (1.9-fold increase). The increase in serum triglyceride levels was sustained for at least 16 h. Serum cholesterol levels were also increased, but the effect was delayed beginning at 4 h, with peak values at 16 h (1.27-fold increase). KGF did not decrease the clearance of triglyceride-rich lipoproteins, but increased hepatic triglyceride secretion. KGF stimulated lipolysis, but not hepatic de novo fatty acid synthesis, and the increased delivery of FFA to the liver plays a crucial role in the KGF-induced hypertriglyceridemia. Neither alpha- nor beta-adrenergic receptor antagonists affected the hypertriglyceridemia induced by KGF, indicating that endogenous catecholamines are not involved in mediating KGF-induced hypertriglyceridemia. These results demonstrate that KGF induces hypertriglyceridemia by increasing hepatic triglyceride secretion, with the fatty acids provided by lipolysis making a major contribution. Thus, KGF could modulate lipid metabolism in vivo.
角质形成细胞生长因子（KGF）是成纤维细胞生长因子家族的一员，最初是从肺成纤维细胞系中分离出来后被鉴定为角质形成细胞有丝分裂原。在本研究中，我们证明给小鼠和大鼠施用KGF会升高血脂水平。在大鼠中，施用KGF后1小时，血清甘油三酯和游离脂肪酸（FFA）水平升高，在2小时达到峰值（增加1.9倍）。血清甘油三酯水平的升高持续至少16小时。血清胆固醇水平也升高，但作用延迟，从4小时开始，在16小时达到峰值（增加1.27倍）。KGF并未降低富含甘油三酯的脂蛋白的清除率，但增加了肝脏甘油三酯的分泌。KGF刺激脂肪分解，但不刺激肝脏从头合成脂肪酸，并且FFA向肝脏的输送增加在KGF诱导的高甘油三酯血症中起关键作用。α-和β-肾上腺素能受体拮抗剂均未影响KGF诱导的高甘油三酯血症，表明内源性儿茶酚胺不参与介导KGF诱导的高甘油三酯血症。这些结果表明，KGF通过增加肝脏甘油三酯分泌诱导高甘油三酯血症，脂肪分解提供的脂肪酸起主要作用。因此，KGF可以在体内调节脂质代谢。
