A pyrexic effect of FGF21 independent of energy expenditure and UCP1,Molecular Metabolism

当前位置： X-MOL 学术 › Mol. Metab. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

A pyrexic effect of FGF21 independent of energy expenditure and UCP1
Molecular Metabolism ( IF 7.0 ) Pub Date : 2021-08-19 , DOI: 10.1016/j.molmet.2021.101324
Petr Zouhar ₁ , Petra Janovska ₁ , Sara Stanic ₁ , Kristina Bardova ₁ , Jiri Funda ₁ , Blanka Haberlova ₁ , Birgitte Andersen ₂ , Martin Rossmeisl ₁ , Barbara Cannon ₃ , Jan Kopecky ₁ , Jan Nedergaard ₃

Affiliation

Objective

Administration of FGF21 to mice reduces body weight and increases body temperature. The increase in body temperature is generally interpreted as hyperthermia, i.e. a condition secondary to the increase in energy expenditure (heat production). Here, we examine an alternative hypothesis: that FGF21 has a direct pyrexic effect, i.e. FGF21 increases body temperature independently of any effect on energy expenditure.

Methods

We studied the effects of FGF21 treatment on body temperature and energy expenditure in high-fat-diet-fed and chow-fed mice exposed acutely to various ambient temperatures, in high-fat diet-fed mice housed at 30 °C (i.e. at thermoneutrality), and in mice lacking uncoupling protein 1 (UCP1).

Results

In every model studied, FGF21 increased body temperature, but energy expenditure was increased only in some models. The effect of FGF21 on body temperature was more (not less, as expected in hyperthermia) pronounced at lower ambient temperatures. Effects on body temperature and energy expenditure were temporally distinct (daytime versus nighttime). FGF21 enhanced UCP1 protein content in brown adipose tissue (BAT); there was no measurable UCP1 protein in inguinal brite/beige adipose tissue. FGF21 increased energy expenditure through adrenergic stimulation of BAT. In mice lacking UCP1, FGF21 did not increase energy expenditure but increased body temperature by reducing heat loss, e.g. a reduced tail surface temperature.

Conclusion

The effect of FGF21 on body temperature is independent of UCP1 and can be achieved in the absence of any change in energy expenditure. Since elevated body temperature is a primary effect of FGF21 and can be achieved without increasing energy expenditure, only limited body weight-lowering effects of FGF21 may be expected.

中文翻译：

FGF21的发热效应与能量消耗和UCP1无关

客观的

向小鼠施用 FGF21 可减轻体重并提高体温。体温升高通常被解释为体温过高，即继发于能量消耗（热量产生）增加的情况。在这里，我们检验了另一种假设：FGF21 具有直接的发热效应，即 FGF21 增加体温，而不受任何对能量消耗的影响。

方法

我们研究了 FGF21 治疗对急性暴露于各种环境温度的高脂肪饮食喂养和食物喂养小鼠的体温和能量消耗的影响，在高脂饮食喂养的小鼠中，饲养在 30°C（即热中性） )，以及缺乏解偶联蛋白 1 (UCP1) 的小鼠。

结果

在所研究的每个模型中，FGF21 都会增加体温，但仅在某些模型中能量消耗会增加。在较低的环境温度下，FGF21 对体温的影响更大（而不是更少，正如在热疗中所预期的那样）。对体温和能量消耗的影响在时间上是不同的（白天与夜间）。FGF21 增强棕色脂肪组织 (BAT) 中的 UCP1 蛋白含量；在腹股沟 brite/米色脂肪组织中没有可测量的 UCP1 蛋白。FGF21 通过对 BAT 的肾上腺素能刺激增加能量消耗。在缺乏 UCP1 的小鼠中，FGF21 不会增加能量消耗，而是通过减少热量损失（例如降低尾巴表面温度）来增加体温。