Using Multiple Analytical Platforms to Investigate the Androgen Depletion Effects on Fecal Metabolites in a Mouse Model of Systemic Lupus Erythematosus.
Using Multiple Analytical Platforms to Investigate the Androgen Depletion Effects on Fecal Metabolites in a Mouse Model of Systemic Lupus Erythematosus.
复制标题
使用多个分析平台研究雄激素消耗对系统性红斑狼疮小鼠模型粪便代谢物的影响。
DOI：
10.1021/acs.jproteome.9b00558
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发表时间：
2020
影响因子：
4.4
通讯作者：
Kosiewicz,MicheleM
中科院分区：
文献类型：
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作者：
Yuan,Fang;Harder,James;Ma,Jing;Yin,Xinmin;Zhang,Xiang;Kosiewicz,MicheleM
系统性红斑狼疮（SLE）是一种自身免疫性疾病，其特征在于循环自身抗体存款在靶器官（例如，肾），导致慢性炎症和最终器官的破坏。在人类和自发性狼疮小鼠模型（如NZBxNZW F1（BWF 1）小鼠）中，SLE在女性中比男性更普遍。通过阉割消耗雄激素显著增加BWF 1男性对狼疮的易感性。我们比较了去势BWF 1（雄激素耗尽）雄性、完整（雄激素充足）雄性和雌性小鼠的粪便代谢产物谱。采用4个分析平台研究了从成年BWF 1小鼠采集的小鼠粪便中极性代谢产物的谱，共鉴定出435种代谢产物。其中，72种代谢物的丰度水平在去势和完整雄性组之间存在显著差异，63种代谢物在雌性和雄性组之间存在差异。途径分析表明，阉割雄性小鼠和完整雄性小鼠之间的途径差异与雌性小鼠和完整雄性小鼠之间的途径差异非常相似，这表明低水平的雄激素，无论是由于消耗（阉割雄性）还是内源性（雌性），都与多种粪便代谢组学变化相关，这可能会影响SLE的进展。我们的研究结果表明，使用多个分析平台分析粪便代谢物对于检测复杂疾病模型系统中的代谢组学改变具有很大的希望。
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by circulating autoantibodies that deposit in target organs (e.g., kidneys), resulting in chronic inflammation and eventual destruction of the organ. SLE is much more prevalent in females than males in both humans and spontaneous mouse models of lupus, such as NZBxNZW F1 (BWF1) mice. Depleting androgens by castration dramatically increases the susceptibility of BWF1 male to lupus. We compared fecal metabolite profiles of castrated BWF1 (androgen-depleted) male, intact (androgen-replete) male, and female mice. Four analytical platforms were employed to study the profiles of polar metabolites in mouse feces collected from adult BWF1 mice, and a total of 435 metabolites was identified. Of these, the abundance levels of 72 metabolites were significantly different between castrated and intact male groups, and 63 metabolites were different between female and male groups. Pathway analysis indicated that the pathway differences between castrated and intact male mice closely resembled the pathway differences between female and intact male mice, suggesting that low levels of androgens, whether due to depletion (castrated male) or endogenous (female), are associated with multiple fecal metabolomic alterations, which could potentially affect SLE progression. Our findings demonstrate that analyzing fecal metabolites using multiple analytical platforms holds great promise for detecting metabolomic alterations in complex disease model systems.