Gene and metabolite expression dependence on body mass index in human myocardium.
Gene and metabolite expression dependence on body mass index in human myocardium.
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DOI：
10.1038/s41598-022-05562-8
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发表时间：
2022-01-26
影响因子：
4.6
通讯作者：
Woźniak MJ
中科院分区：
文献类型：
--
作者：
Adebayo AS;Roman M;Zakkar M;Yusoff S;Gulston M;Joel-David L;Anthony B;Lai FY;Murgia A;Eagle-Hemming B;Sheikh S;Kumar T;Aujla H;Dott W;Griffin JL;Murphy GJ;Woźniak MJ
我们假设体重指数（BMI）依赖性心肌基因表达和能量相关代谢物的变化是心脏手术中BMI和死亡率（肥胖悖论）之间双相关联的基础。我们进行了转录组分析，并测量了一组144种代谢物，分别在53和55个心肌活检组织中，来自一组66名接受冠状动脉旁路移植术的成年患者（注册号：NCT 02908009）。初步分析确定了239个转录与双相BMI依赖。120例呈u型，119例呈n型。确定的局部最小值或最大值在BMI 28-29时达到峰值。根据这些结果，为了最好地符合WHO分类，我们将患者分为三组：BMI < 25，25 ≤ BMI ≤ 32和BMI > 32。分析表明，与BMI < 25的患者相比，25 ≤ BMI ≤ 32的患者蛋白质代谢相关途径下调。在25例≤ BMI ≤ 32的患者中，肌肉收缩转录物上调，在BMI > 32的患者中，胆固醇合成和先天免疫转录物上调。参与翻译、肌肉收缩和脂质代谢的转录本也与BMI的双相依赖性形成了不同的相关网络。代谢物分析表明，BMI > 32组中酰基肉毒碱和5-磷酸核糖增加，BMI < 25组中α-酮戊二酸增加。心肌的分子差异反映了BMI和死亡率之间的双相关系。
We hypothesized that body mass index (BMI) dependent changes in myocardial gene expression and energy-related metabolites underlie the biphasic association between BMI and mortality (the obesity paradox) in cardiac surgery. We performed transcriptome profiling and measured a panel of 144 metabolites in 53 and 55, respectively, myocardial biopsies from a cohort of sixty-six adult patients undergoing coronary artery bypass grafting (registration: NCT02908009). The initial analysis identified 239 transcripts with biphasic BMI dependence. 120 displayed u-shape and 119 n-shape expression patterns. The identified local minima or maxima peaked at BMI 28–29. Based on these results and to best fit the WHO classification, we grouped the patients into three groups: BMI < 25, 25 ≤ BMI ≤ 32, and BMI > 32. The analysis indicated that protein translation-related pathways were downregulated in 25 ≤ BMI ≤ 32 compared with BMI < 25 patients. Muscle contraction transcripts were upregulated in 25 ≤ BMI ≤ 32 patients, and cholesterol synthesis and innate immunity transcripts were upregulated in the BMI > 32 group. Transcripts involved in translation, muscle contraction and lipid metabolism also formed distinct correlation networks with biphasic dependence on BMI. Metabolite analysis identified acylcarnitines and ribose-5-phosphate increasing in the BMI > 32 group and α-ketoglutarate increasing in the BMI < 25 group. Molecular differences in the myocardium mirror the biphasic relationship between BMI and mortality.
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影响因子：
14.9
作者：
Ritchie ME;Phipson B;Wu D;Hu Y;Law CW;Shi W;Smyth GK
通讯作者：
Smyth GK
影响因子：
14.9
作者：
Gene Ontology Consortium
通讯作者：
Gene Ontology Consortium
影响因子：
9.1
作者：
Park J;Ahmadi SF;Streja E;Molnar MZ;Flegal KM;Gillen D;Kovesdy CP;Kalantar-Zadeh K
通讯作者：
Kalantar-Zadeh K
WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
影响因子：
5.6
作者：
Markandran K;Poh JW;Ferenczi MA;Cheung C
通讯作者：
Cheung C