Charles Perkins Centre, University of Sydney, Sydney 2006, Australia; Ageing and Alzheimers Institute, Centre for Education and Research on Ageing, ANZAC Research Institute, Concord Hospital, University of Sydney, Sydney 2139, Australia; School of Life and Environmental Sciences, University of Sydney, Sydney 2006, Australia.
Charles Perkins Centre, University of Sydney, Sydney 2006, Australia; Ageing and Alzheimers Institute, Centre for Education and Research on Ageing, ANZAC Research Institute, Concord Hospital, University of Sydney, Sydney 2139, Australia; Faculty of Medicine, University of Sydney, Sydney 2006, Australia.
Cell Metab. 2016 Oct 11;24(4):555-565. doi: 10.1016/j.cmet.2016.09.001. Epub 2016 Sep 29.
Fibroblast growth factor 21 (FGF21) is the first known endocrine signal activated by protein restriction. Although FGF21 is robustly elevated in low-protein environments, increased FGF21 is also seen in various other contexts such as fasting, overfeeding, ketogenic diets, and high-carbohydrate diets, leaving its nutritional context and physiological role unresolved and controversial. Here, we use the Geometric Framework, a nutritional modeling platform, to help reconcile these apparently conflicting findings in mice confined to one of 25 diets that varied in protein, carbohydrate, and fat content. We show that FGF21 was elevated under low protein intakes and maximally when low protein was coupled with high carbohydrate intakes. Our results explain how elevation of FGF21 occurs both under starvation and hyperphagia, and show that the metabolic outcomes associated with elevated FGF21 depend on the nutritional context, differing according to whether the animal is in a state of under- or overfeeding.
成纤维细胞生长因子 21（FGF21）是第一个被发现的由蛋白质限制激活的内分泌信号。尽管 FGF21 在低蛋白环境中显著升高，但在其他各种情况下也会看到 FGF21 的增加，例如禁食、过度喂养、生酮饮食和高碳水化合物饮食，这使得其营养背景和生理作用仍未得到解决和存在争议。在这里，我们使用几何框架，一个营养建模平台，来帮助调和这些在限制于 25 种不同蛋白质、碳水化合物和脂肪含量的饮食中的老鼠之间的明显冲突的发现。我们表明，FGF21 在低蛋白摄入量下升高，并在低蛋白与高碳水化合物摄入量结合时达到最大值。我们的结果解释了 FGF21 如何在饥饿和过度进食时都升高，并表明与升高的 FGF21 相关的代谢结果取决于营养背景，根据动物是处于饥饿状态还是过度喂养状态而有所不同。
