Early changes in immune cell metabolism and function are a hallmark of sleeve gastrectomy: a prospective human study.
Early changes in immune cell metabolism and function are a hallmark of sleeve gastrectomy: a prospective human study.
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免疫细胞代谢和功能的早期变化是袖状胃切除术的标志：一项前瞻性人体研究。
DOI：
10.1101/2020.07.31.20161687
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Tavakk
中科院分区：
文献类型：
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作者：
Lo,Tammy;Rudge,EleanorJM;Chase,RobertP;Subramaniam,Renuka;Heshmati,Keyvan;Lucey,ElizabethM;Weigl,AlisonM;Iyoha-Bello,OtatadeJ;Ituah,ChelseaO;Benjamin,EmilyJ;McNutt,SethW;Sathe,Leena;Farnam,Leanna;Raby,BenjaminA;Tavakk
目的探讨腹腔镜袖胃切除术（LSG）后血液生物标志物、白细胞组成和基因表达的纵向变化。背景：LSG是一种有效的肥胖治疗方法，可导致持续的体重减轻，改善肥胖相关的合并症和炎症。然而，枸杞多糖对免疫功能和代谢的影响尚不清楚。方法前瞻性资料来自同一机构的23名入组受试者。从术前基线到1年，以3个月的随访间隔观察体重参数、合并症、血液生物标志物和白细胞亚群的趋势。对研究的前6名受试者（基线和术后3个月）的成对全血样本进行rna测序，以确定与接受LSG相关的全基因组基因表达变化。结果：LSG在3个月时导致平均总体重减轻（18.1%）显著降低，糖尿病患者的HbA1c降低。临床炎症和激素生物标志物的改善早在LSG后3个月就得到了证实。中性粒细胞与淋巴细胞比例的减少是由绝对中性粒细胞计数的减少引起的。差异全血基因表达的基因集富集分析表明，3个月后，LSG不仅诱导了炎症细胞因子通路的转录组变化，还诱导了与能量代谢相关的几个关键代谢通路的转录组变化。结论早在术后3个月，LSG就能引起免疫细胞组成和代谢的显著变化。需要进一步评估减肥手术对免疫代谢的影响以及对宿主防御和代谢疾病的影响。
Objective To characterize longitudinal changes in blood biomarkers, leukocyte composition, and gene expression following laparoscopic sleeve gastrectomy (LSG). Background LSG is an effective treatment for obesity, leading to sustainable weight loss and improvements in obesity-related co-morbidities and inflammatory profiles. However, the effects of LSG on immune function and metabolism remain uncertain. Methods Prospective data was collected from 23 enrolled human subjects from a single institution. Parameters of weight, co-morbidities, and trends in blood biomarkers and leukocyte subsets were observed from pre-operative baseline to one year in three-month follow-up intervals. RNA-sequencing was performed on pairs of whole blood samples from the first six subjects of the study (baseline and three months post-surgery) to identify genome-wide gene expression changes associated with undergoing LSG. Results LSG led to a significant decrease in mean total body weight loss (18.1%) at three months and among diabetic subjects a reduction in HbA1c. Improvements in clinical inflammatory and hormonal biomarkers were demonstrated as early as three months after LSG. A reduction in neutrophil-lymphocyte ratio was observed, driven by a reduction in absolute neutrophil counts. Gene set enrichment analyses of differential whole blood gene expression demonstrated that after three months, LSG induced transcriptomic changes not only in inflammatory cytokine pathways but also in several key metabolic pathways related to energy metabolism. Conclusions LSG induces significant changes in the composition and metabolism of immune cells as early as three months post-operatively. Further evaluation is required of bariatric surgery’s effects on immunometabolism and consequences for host defense and metabolic disease.