Department of Biochemistry and Molecular Biology, Dalhousie University, Dalhousie Medicine New Brunswick, Saint John, NB, Canada.
IMPART Investigator Team Canada, Saint John, NB, Canada.
Front Endocrinol (Lausanne). 2020 Aug 7;11:534. doi: 10.3389/fendo.2020.00534. eCollection 2020.
Predicting relapses of post-operative complications in obese patients who undergo cardiac surgery is significantly complicated by persistent metabolic maladaptation associated with obesity. Despite studies supporting the linkages of increased systemic branched-chain amino acids (BCAAs) driving the pathogenesis of obesity, metabolome wide studies have either supported or challenged association of circulating BCAAs with cardiovascular diseases (CVDs). We interrogated whether BCAA catabolic changes precipitated by obesity in the heart and adipose tissue can be reliable prognosticators of adverse outcomes following cardiac surgery. Our study specifically clarified the correlation between BCAA catabolizing enzymes, cellular BCAAs and branched-chain keto acids (BCKAs) with the severity of cardiometabolic outcomes in obese patients pre and post cardiac surgery. Male and female patients of ages between 44 and 75 were stratified across different body mass index (BMI) (non-obese = 17, pre-obese = 19, obese class I = 14, class II = 17, class III = 12) and blood, atrial appendage (AA), and subcutaneous adipose tissue (SAT) collected during cardiac surgery. Plasma and intracellular BCAAs and BC ketoacids (BCKAs), tissue mRNA and protein expression and activity of BCAA catabolizing enzymes were assessed and correlated with clinical parameters. Intramyocellular, but not systemic, BCAAs increased with BMI in cardiac surgery patients. In SAT, from class III obese patients, mRNA and protein expression of BCAA catabolic enzymes and BCKA dehydrogenase (BCKDH) enzyme activity was decreased. Within AA, a concomitant increase in mRNA levels of BCAA metabolizing enzymes was observed, independent of changes in BCKDH protein expression or activity. BMI, indices of tissue dysfunction and duration of hospital stay following surgery correlated with BCAA metabolizing enzyme expression and metabolite levels in AA and SAT. This study proposes that in a setting of obesity, dysregulated BCAA catabolism could be an effective surrogate to determine cardiac surgery outcomes and plausibly predict premature re-hospitalization.
预测接受心脏手术后肥胖患者术后并发症的复发，由于与肥胖相关的持续代谢适应不良而变得非常复杂。尽管有研究支持增加的系统性支链氨基酸（BCAAs）与肥胖的发病机制有关，但代谢组学研究既支持也挑战了循环 BCAAs 与心血管疾病（CVDs）的关联。我们探讨了肥胖在心脏和脂肪组织中引起的支链氨基酸分解代谢变化是否可以作为心脏手术后不良结局的可靠预后指标。我们的研究特别阐明了心脏手术前后肥胖患者中支链氨基酸分解代谢酶、细胞内支链氨基酸和支链酮酸（BCKAs）与心脏代谢结局严重程度之间的相关性。研究纳入了年龄在 44 至 75 岁之间的男性和女性患者，按不同的身体质量指数（BMI）分层（非肥胖=17，超重=19，肥胖 I 级=14，肥胖 II 级=17，肥胖 III 级=12），并在心脏手术期间收集血液、心房附件（AA）和皮下脂肪组织（SAT）。评估了血浆和细胞内支链氨基酸和支链酮酸（BCKAs）、组织 mRNA 和蛋白质表达以及支链氨基酸分解代谢酶的活性，并与临床参数相关联。在心脏手术患者中，肌内而非系统性的支链氨基酸随着 BMI 的增加而增加。在 SAT 中，来自肥胖 III 级患者的支链氨基酸分解代谢酶的 mRNA 和蛋白质表达以及 BCKA 脱氢酶（BCKDH）酶活性降低。在 AA 中，观察到支链氨基酸代谢酶的 mRNA 水平同时升高，与 BCKDH 蛋白表达或活性的变化无关。BMI、组织功能障碍指标和手术后住院时间与 AA 和 SAT 中支链氨基酸代谢酶表达和代谢物水平相关。这项研究表明，在肥胖的情况下，支链氨基酸分解代谢的失调可能是确定心脏手术结果的有效替代指标，并可能预测过早重新住院。
