PDF(Pubmed)
Abstract：
BACKGROUND: Home parenteral nutrition (HPN) is often cycled nocturnally and is expected to result in glucose intolerance and sleep disruption partly due to circadian misalignment. This study aimed to define the metabolic response when HPN is cycled during the daytime compared to overnight.
METHODS: This secondary analysis leveraged samples from a clinical trial in adults with short bowel syndrome consuming HPN (ClinicalTrials.gov: NCT04743960). Enrolled patients received 1 week of HPN overnight followed by 1 week of HPN during the daytime. Fasting blood samples were collected following each study period and global metabolic profiles were examined from plasma samples. Differential metabolite abundance was determined from normalized and scaled data using adjusted Linear Models for MicroArray Data models followed by pathway enrichment analysis.
RESULTS: Nine patients (mean age, 52.6 years; 78% female; mean BMI 20.7 kg/m2) provided samples. Among 622 identified metabolites, changes were observed in 36 metabolites at Punadj < 0.05 with higher abundance of fatty acids, long-chain and polyunsaturated fatty acids (Dihomo-gamma-linolenic acid, arachidonate (20:4n6), docosahexaenoate (DHA; 22:6n3)) and glycerolipids with daytime infusions. Enrichment analysis identified changes in pathways related to the biosynthesis of unsaturated fatty acids, d-arginine, and d-ornithine metabolism, and linoleic acid metabolism (Punadj<0.05).
CONCLUSIONS: Daytime infusions of HPN may result in changes in circulating lipids and amino acid composing metabolic pathways previously implicated in circadian rhythms. As this is the first untargeted metabolomics study of HPN, larger studies are needed.
METHODS: This secondary analysis leveraged samples from a clinical trial in adults with short bowel syndrome consuming HPN (ClinicalTrials.gov: NCT04743960). Enrolled patients received 1 week of HPN overnight followed by 1 week of HPN during the daytime. Fasting blood samples were collected following each study period and global metabolic profiles were examined from plasma samples. Differential metabolite abundance was determined from normalized and scaled data using adjusted Linear Models for MicroArray Data models followed by pathway enrichment analysis.
RESULTS: Nine patients (mean age, 52.6 years; 78% female; mean BMI 20.7 kg/m2) provided samples. Among 622 identified metabolites, changes were observed in 36 metabolites at Punadj < 0.05 with higher abundance of fatty acids, long-chain and polyunsaturated fatty acids (Dihomo-gamma-linolenic acid, arachidonate (20:4n6), docosahexaenoate (DHA; 22:6n3)) and glycerolipids with daytime infusions. Enrichment analysis identified changes in pathways related to the biosynthesis of unsaturated fatty acids, d-arginine, and d-ornithine metabolism, and linoleic acid metabolism (Punadj<0.05).
CONCLUSIONS: Daytime infusions of HPN may result in changes in circulating lipids and amino acid composing metabolic pathways previously implicated in circadian rhythms. As this is the first untargeted metabolomics study of HPN, larger studies are needed.
摘要：
背景：家庭肠外营养（HPN）通常在夜间循环，预计会导致葡萄糖不耐受和睡眠中断，部分原因是昼夜节律失调。这项研究旨在定义与过夜相比，白天循环HPN时的代谢反应。
方法：本二级分析利用了在患有消耗HPN的短肠综合征的成人中进行的临床试验的样本（ClinicalTrials.gov：NCT04743960）。纳入的患者接受1周的HPN过夜，然后在白天接受1周的HPN。在每个研究阶段后收集空腹血样,并从血浆样品中检查总体代谢谱。使用经调整的用于微阵列数据模型的线性模型,然后进行途径富集分析,从归一化和缩放数据确定差异代谢物丰度。
结果：9名患者（平均年龄，52.6岁；78%为女性；平均BMI20.7kg/m2）提供样本。在622种确定的代谢物中，在Punadj<0.05观察到36种代谢物的变化，脂肪酸的丰度更高，长链和多不饱和脂肪酸(二高-γ-亚麻酸，花生（20:4n6），二十二碳六烯酸酯（DHA；22：6n3））和甘油脂，白天输注。富集分析确定了与不饱和脂肪酸生物合成相关的途径的变化，d-精氨酸,和d-鸟氨酸代谢，和亚油酸代谢(Punadj<0.05)。
结论：白天输注HPN可能导致先前与昼夜节律有关的循环脂质和氨基酸组成代谢途径的变化。由于这是HPN的首次非靶向代谢组学研究，需要更大的研究。
方法：本二级分析利用了在患有消耗HPN的短肠综合征的成人中进行的临床试验的样本（ClinicalTrials.gov：NCT04743960）。纳入的患者接受1周的HPN过夜，然后在白天接受1周的HPN。在每个研究阶段后收集空腹血样,并从血浆样品中检查总体代谢谱。使用经调整的用于微阵列数据模型的线性模型,然后进行途径富集分析,从归一化和缩放数据确定差异代谢物丰度。
结果：9名患者（平均年龄，52.6岁；78%为女性；平均BMI20.7kg/m2）提供样本。在622种确定的代谢物中，在Punadj<0.05观察到36种代谢物的变化，脂肪酸的丰度更高，长链和多不饱和脂肪酸(二高-γ-亚麻酸，花生（20:4n6），二十二碳六烯酸酯（DHA；22：6n3））和甘油脂，白天输注。富集分析确定了与不饱和脂肪酸生物合成相关的途径的变化，d-精氨酸,和d-鸟氨酸代谢，和亚油酸代谢(Punadj<0.05)。
结论：白天输注HPN可能导致先前与昼夜节律有关的循环脂质和氨基酸组成代谢途径的变化。由于这是HPN的首次非靶向代谢组学研究，需要更大的研究。
