Abstract
Background: 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).Objective: 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.Methods: 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.Results: 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.Conclusion: 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.
Highlights
Current estimates suggest that >35% of patients undergoing heart surgery are obese (body mass index (BMI) >30 kg/m2) [1]
Patients with a BMI of 18.5–24.9 kg/m2 were considered as the non-obese control group (n = 17), patients with a BMI of 25.0–29.9 kg/m2 were classified as pre-obese (n = 19), patients with a BMI of 30–34.9 kg/m2 were classified as class I obese (n = 14), patients with a BMI of 35.0–39.9 kg/m2 were classified as class II obese (n = 17) and patients with a BMI of ≥40 kg/m2 were classified as class III obese (n = 12)
Contrary to rodent studies demonstrating an increase in circulating branched-chain amino acid (BCAA) due to downregulation of adipose BCAA catabolic enzymes [41], BCAA catabolizing enzyme expression remodeling in subcutaneous adipose tissue (SAT) of obese cardiac surgery patients in our study did not reflect in changes in plasma BCAA levels
Summary
Current estimates suggest that >35% of patients undergoing heart surgery are obese (body mass index (BMI) >30 kg/m2) [1]. Predicting relapses of post-operative complications in obese patients who undergo cardiac surgery is significantly complicated by persistent metabolic maladaptation associated with obesity, such as increases in circulating lipids, glucose, adipocytokines (leptin, insulin, RBP4) and branch chain amino acids (BCAAs). Multiple metabolome wide studies of ischemic heart disease [19, 20] myocardial infarction [21] and incident coronary artery disease [22, 23] have failed to attribute elevated BCAAs for driving CVD. 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)
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