Distinct Metabolic States Are Observed in Hypoglycemia Induced in Mice by Ricin Toxin or by Fasting.
Distinct Metabolic States Are Observed in Hypoglycemia Induced in Mice by Ricin Toxin or by Fasting.
复制标题
在蓖麻毒素或禁食诱导的小鼠低血糖症中观察到不同的代谢状态
DOI：
10.3390/toxins14120815
复制
发表时间：
2022-11-22
期刊：
影响因子：
4.2
通讯作者：
Pincus SH
中科院分区：
文献类型：
--
作者：
Kempa J;O'Shea-Stone G;Moss CE;Peters T;Marcotte TK;Tripet B;Eilers B;Bothner B;Copié V;Pincus SH
低血糖可由多种生理和病理刺激诱发，如果不治疗可导致危及生命的后果。然而，低血糖也可能在间歇性禁食和热量限制的健康益处中发挥作用。先前，我们证明了全身性给予蓖麻毒素诱导小鼠致命性低血糖。在这里，我们研究了两种不同刺激在小鼠肝脏中诱导的低血糖状态的代谢景观：全身性蓖麻毒素给药和禁食。每种刺激都产生相同的血糖降低和体重减轻。使用1H NMR对极性代谢物组进行了研究，定量了59种特定代谢物，并使用非靶向LC-MS对约5000种特征进行了研究。结果进行了多变量分析，使用主成分分析（PCA）和偏最小二乘判别分析（PLS-DA），以确定全球的代谢模式，并通过单变量分析（ANOVA），以评估个别代谢物。结果表明，虽然对两种刺激的反应有一些相似之处，包括降低葡萄糖，ADP和谷胱甘肽，但它们引起了不同的代谢状态。显示最大差异的代谢物是O-磷酸胆碱，在蓖麻毒素处理的动物中升高，并且已知受促炎细胞因子TNF-α的影响。另一个不同之处是所使用的替代燃料来源，禁食引起的低血糖主要是酮症的，而对蓖麻毒素引起的低血糖的反应涉及蛋白质和氨基酸催化剂。
Hypoglycemia may be induced by a variety of physiologic and pathologic stimuli and can result in life-threatening consequences if untreated. However, hypoglycemia may also play a role in the purported health benefits of intermittent fasting and caloric restriction. Previously, we demonstrated that systemic administration of ricin toxin induced fatal hypoglycemia in mice. Here, we examine the metabolic landscape of the hypoglycemic state induced in the liver of mice by two different stimuli: systemic ricin administration and fasting. Each stimulus produced the same decrease in blood glucose and weight loss. The polar metabolome was studied using 1H NMR, quantifying 59 specific metabolites, and untargeted LC-MS on approximately 5000 features. Results were analyzed by multivariate analyses, using both principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA), to identify global metabolic patterns, and by univariate analyses (ANOVA) to assess individual metabolites. The results demonstrated that while there were some similarities in the responses to the two stimuli including decreased glucose, ADP, and glutathione, they elicited distinct metabolic states. The metabolite showing the greatest difference was O-phosphocholine, elevated in ricin-treated animals and known to be affected by the pro-inflammatory cytokine TNF-α. Another difference was the alternative fuel source utilized, with fasting-induced hypoglycemia primarily ketotic, while the response to ricin-induced hypoglycemia involves protein and amino acid catabolism.
登录
查看更多内容
DOI：
10.2165/00139709-200322010-00006
发表时间：
2003-01-01
期刊：
Toxicological Reviews
影响因子：
--
作者：
Lord, Michael J.;Jolliffe, Nicholas A.;Roberts, Lynne M.
通讯作者：
Roberts, Lynne M.
影响因子：
4.2
作者：
Pincus SH;Kyro A;Maresh GA;Peters T;Kempa J;Marcotte TK;Gao Z;Ye J;Copié V;Song K
通讯作者：
Song K
影响因子：
4.4
作者：
Lindauer, Meghan L.;Wong, John;Magun, Bruce E.
通讯作者：
Magun, Bruce E.
影响因子：
9.8
作者：
CHAJEKSHAUL, T;BARASH, V;SHILONI, E
通讯作者：
SHILONI, E
影响因子：
3.6
作者：
D'Elia, Riccardo, V;Goodchild, Sarah A.;Dunn, Warwick B.
通讯作者：
Dunn, Warwick B.