Metabolic profiling reveals an abnormal pattern of serum fatty acids in MRL/lpr mice under treatment with prednisone
Metabolic profiling reveals an abnormal pattern of serum fatty acids in MRL/lpr mice under treatment with prednisone
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代谢分析揭示了接受泼尼松治疗的 MRL/lpr 小鼠血清脂肪酸的异常模式
DOI：
10.3389/fphar.2020.00115
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发表时间：
2020
影响因子：
5.6
通讯作者：
Dehong Wu
中科院分区：
文献类型：
--
作者：
Qianqian Li;Jia Zhou;Dingyi Zhang;Xiafeng Zhang;Zhenghao Xu;Dehong Wu
糖皮质激素（GC）通常用于治疗系统性红斑狼疮（SLE）。不幸的是，过多的GC会引起许多与脂肪酸（FA）代谢紊乱相关的副作用。虽然GC处理后总FA水平增加，但尚不清楚是所有FA种类增加还是仅某些FA种类改变。采用气相色谱-质谱联用技术，观察了5 mg/kg泼尼松对SLE模型小鼠（MRL/lpr）血清中FA种类的影响。该研究显示，与对照组相比，MRL/lpr小鼠中的FA谱不同，主要表现为多不饱和FA（花生四烯酸、二十二碳六烯酸等）升高，与炎症状态相关;以及改变的（产物FA/前体FA）比率，代表FA去饱和酶和延伸酶的估计活性（多种延伸酶、△4去饱和酶、△5去饱和酶、△6去饱和酶的活性较高，△8去饱和酶的活性较低）。5 mg/kg泼尼松治疗可降低MRL/lpr小鼠的n-6多不饱和脂肪酸总水平，尤其是花生四烯酸水平和△5去饱和酶估计活性降至对照水平。此外，泼尼松诱导额外的扰动脂肪酸，不仅包括饱和脂肪酸，但也单不饱和脂肪酸和n-3多不饱和脂肪酸，表明有一个强大的影响，泼尼松对脂肪酸代谢。这些结果可能对进一步研究GCs治疗的副作用有价值。
Glucocorticoids (GCs) are commonly used to treat systemic lupus erythematosus (SLE). Unfortunately, excessive GCs can induce many side effects associated with disordered fatty acid (FA) metabolism. Although an increased level of total FA has been found after GCs treatment, it is not clear whether all FA species increased or only certain FA species were altered. A gas chromatography–mass spectrometry-based FA profiling approach was performed to reveal the alterations of FA species in SLE model mice (MRL/lpr) after treatment with 5 mg/kg of prednisone. The study showed a distinct FA profile in MRL/lpr mice compared to the controls, mainly manifested by elevated polyunsaturated FAs (arachidonate, docosahexaenoate, etc.), which are related to the inflammatory state; and altered (product FA/precursor FA) ratios representing the estimated activities of FA desaturase and elongase (higher activities of multiple elongases, △4 desaturase, △5 desaturase, △6 desaturase, and lower activity of △8 desaturase). Treatment with 5 mg/kg of prednisone decreased the total level of n-6 polyunsaturated FA in MRL/lpr mice; in particular, the level of arachidonate and estimated activity of △5 desaturase were reduced to the control level. Moreover, prednisone induced additional perturbations in FAs, including not only saturated FAs, but also monounsaturated FAs and n-3 polyunsaturated FAs, indicating that there was a strong effect of prednisone on FA metabolism. These results may be valuable for further studies of the side effects of GCs treatment.