Murata Yusuke, Konishi Morichika, Itoh Nobuyuki
Department of Genetic Biochemistry, Kyoto University Graduate School of Pharmaceutical Sciences, Sakyo, Kyoto 606-8501, Japan.
J Nutr Metab. 2011;2011:981315. doi: 10.1155/2011/981315. Epub 2011 Feb 6.
The FGF family comprises twenty-two structurally related proteins with functions in development and metabolism. The Fgf21 gene was generated early in vertebrate evolution. FGF21 acts as an endocrine regulator in lipid metabolism. Hepatic Fgf21 expression is markedly induced in mice by fasting or a ketogenic diet. Experiments with Fgf21 transgenic mice and cultured cells indicate that FGF21 exerts pharmacological effects on glucose and lipid metabolism in hepatocytes and adipocytes via cell surface FGF receptors. However, experiments with Fgf21 knockout mice indicate that FGF21 inhibits lipolysis in adipocytes during fasting and attenuates torpor induced by a ketogenic diet but maybe not a physiological regulator for these hepatic functions. These findings suggest the pharmacological effects to be distinct from the physiological roles. Serum FGF21 levels are increased in patients with metabolic diseases having insulin resistance, indicating that FGF21 is a metabolic regulator and a biomarker for these diseases.
FGF家族由22种结构相关的蛋白质组成，在发育和代谢过程中发挥作用。Fgf21基因在脊椎动物进化早期产生。FGF21作为脂质代谢中的一种内分泌调节因子。禁食或生酮饮食可显著诱导小鼠肝脏Fgf21表达。对Fgf21转基因小鼠和培养细胞进行的实验表明，FGF21通过细胞表面FGF受体对肝细胞和脂肪细胞的葡萄糖和脂质代谢发挥药理作用。然而，对Fgf21基因敲除小鼠进行的实验表明，FGF21在禁食期间抑制脂肪细胞中的脂肪分解，并减轻生酮饮食诱导的蛰伏，但可能不是这些肝脏功能的生理调节因子。这些发现表明药理作用与生理作用不同。胰岛素抵抗的代谢疾病患者血清FGF21水平升高，表明FGF21是这些疾病的代谢调节因子和生物标志物。
