Division of Endocrinology and Metabolism, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA.
Division of Endocrinology and Metabolism, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA ; Broad Institute, Cambridge, MA 02142, USA.
Mol Metab. 2014 Oct 8;4(1):51-7. doi: 10.1016/j.molmet.2014.09.008. eCollection 2015 Jan.
Fibroblast growth factor 21 (FGF21) is a hormone with pleiotropic metabolic activities which, in rodents, is robustly regulated by fasting and ketogenic diets. In contrast, similar dietary interventions have either no or minimal effects on circulating FGF21 in humans. Moreover, no intervention or dietary challenge has been shown to acutely stimulate circulating FGF21 in either humans or animals. Recent animal data suggest that the transcription factor Carbohydrate Responsive-Element Binding Protein (ChREBP) stimulates hepatic FGF21 expression and that fructose may activate hepatic ChREBP more robustly than glucose. Here, we examined whether fructose ingestion can acutely stimulate FGF21 in humans.
We measured serum FGF21, glucose, insulin, and triglyceride levels in ten lean, healthy adults and eleven adults with the metabolic syndrome following oral ingestion of 75 g of glucose, fructose, or a combination of the two sugars.
FGF21 levels rose rapidly following fructose ingestion, achieved a mean 3.4-fold increase at two hours (P < 0.01), and returned to baseline levels within five hours. In contrast, FGF21 did not increase in the first two hours following ingestion of a glucose load, although more modest increases were observed after three to four hours. Both baseline and fructose-stimulated FGF21 levels were 2-3 fold elevated in subjects with metabolic syndrome.
Fructose ingestion acutely and robustly increases serum FGF21 levels in humans in a pattern consistent with a hormonal response. While FGF21 appears to be critical for the adaptive response to fasting or starvation in rodents, these findings suggest that in humans, FGF21 may play an important role in fructose metabolism.
成纤维细胞生长因子 21（FGF21）是一种具有多种代谢活性的激素，在啮齿动物中，它受到禁食和生酮饮食的强烈调节。相比之下，类似的饮食干预对人体循环中的 FGF21 几乎没有影响。此外，无论是在人类还是动物中，都没有干预或饮食挑战能够急性刺激循环中的 FGF21。最近的动物数据表明，转录因子碳水化合物反应元件结合蛋白（ChREBP）刺激肝 FGF21 的表达，并且果糖可能比葡萄糖更有效地激活肝 ChREBP。在这里，我们研究了果糖摄入是否可以在人类中急性刺激 FGF21。
我们在 10 名瘦的健康成年人和 11 名代谢综合征患者中测量了口服 75g 葡萄糖、果糖或两种糖的混合物后血清 FGF21、葡萄糖、胰岛素和甘油三酯水平。
果糖摄入后 FGF21 水平迅速升高，在两小时时达到平均 3.4 倍的增加（P<0.01），并在五小时内恢复到基线水平。相比之下，在摄入葡萄糖负荷后的前两小时内，FGF21 没有增加，尽管在三到四小时后观察到更温和的增加。在代谢综合征患者中，基线和果糖刺激的 FGF21 水平均升高 2-3 倍。
果糖摄入在人类中急性且强烈地增加血清 FGF21 水平，其模式与激素反应一致。虽然 FGF21 似乎对啮齿动物的禁食或饥饿适应至关重要，但这些发现表明，在人类中，FGF21 可能在果糖代谢中发挥重要作用。
