School of Life Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, NG7 2UH, UK.
Lilly Research Laboratories, Indianapolis, IN, 46285, USA.
Sci Rep. 2017 Jun 26;7(1):4238. doi: 10.1038/s41598-017-03607-x.
FGF21 exerts profound metabolic effects in Siberian hamsters exposed to long day (LD) photoperiods that increase appetite and adiposity, however these effects are attenuated in short day (SD) animals that display hypophagia and reduced adiposity. The aim of this study was to investigate whether the beneficial effects of a novel mimetic of FGF21 in the LD state are a consequence of increased adiposity or of the central photoperiodic state. This was achieved by investigating effects of FGF21 in aged hamsters, which is associated with reduced adiposity. In LD hamsters with increased adiposity, FGF21 lowered body weight as a result of both reduced daily food intake and increased caloric expenditure, driven by an increase in whole-body fat oxidation. However, in LD animals with reduced adiposity, the effect of FGF21 on body weight, caloric intake and fat oxidation were significantly attenuated or absent when compared to those with increased adiposity. These attenuated/absent effects were underpinned by the inability of FGF21 to increase the expression of key thermogenic genes in interscapular and visceral WAT. Our study demonstrates the efficacy of a novel FGF21 mimetic in hamsters, but reveals attenuated effects in the animal model where adiposity is reduced naturally independent of photoperiod.
成纤维细胞生长因子 21 (FGF21) 在暴露于长日照 (LD) 光周期的西伯利亚仓鼠中发挥着深刻的代谢作用，增加食欲和脂肪堆积，但这些作用在表现出食欲减退和脂肪减少的短日照 (SD) 动物中减弱。本研究的目的是探讨一种新型 FGF21 类似物在 LD 状态下的有益作用是由于脂肪堆积增加还是由于中央光周期状态所致。这是通过研究 FGF21 在老年仓鼠中的作用来实现的，老年仓鼠与脂肪减少有关。在 LD 中脂肪堆积增加的仓鼠中，FGF21 通过减少每日食物摄入量和增加热量消耗来降低体重，这是由全身脂肪氧化增加驱动的。然而，在 LD 中脂肪减少的动物中，与脂肪堆积增加的动物相比，FGF21 对体重、热量摄入和脂肪氧化的影响明显减弱或不存在。这些减弱/不存在的作用是由于 FGF21 不能增加肩胛间和内脏白色脂肪组织中关键产热基因的表达。我们的研究表明了一种新型 FGF21 类似物在仓鼠中的功效，但揭示了在自然减少脂肪堆积而不依赖于光周期的动物模型中，作用减弱。
