Reduced adiposity attenuates FGF21 mediated metabolic improvements in the Siberian hamster.
Reduced adiposity attenuates FGF21 mediated metabolic improvements in the Siberian hamster.
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DOI：
10.1038/s41598-017-03607-x
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发表时间：
2017-06-26
影响因子：
4.6
通讯作者：
Ebling FJP
中科院分区：
文献类型：
--
作者：
Lewis JE;Samms RJ;Cooper S;Luckett JC;Perkins AC;Adams AC;Tsintzas K;Ebling FJP
FGF 21在暴露于长日照（LD）光周期的西伯利亚仓鼠中发挥了显著的代谢作用，增加食欲和肥胖，然而这些作用在表现出食欲减退和肥胖减少的短日照（SD）动物中减弱。本研究的目的是调查是否在LD状态的FGF 21的一种新的模拟物的有益效果是增加的肥胖或中央光周期状态的结果。这是通过研究FGF 21在老年仓鼠中的作用来实现的，这与肥胖减少有关。在肥胖增加的LD仓鼠中，FGF 21降低了体重，这是由于每日食物摄入量减少和热量消耗增加，这是由全身脂肪氧化增加驱动的。然而，在具有减少的肥胖的LD动物中，当与具有增加的肥胖的那些相比时，FGF 21对体重、热量摄入和脂肪氧化的作用显著减弱或不存在。这些减弱/缺失的作用是由于FGF 21无法增加肩胛间和内脏WAT中关键产热基因的表达。我们的研究证明了一种新的FGF 21模拟物在仓鼠中的功效，但在动物模型中显示了减弱的作用，其中肥胖症不依赖于光周期而自然减少。
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.