Identification of Metabolite Shifts and Early Serum Predictors for Indicators of Remodelling in Diabetes and Nondiabetic Models of Cardiac Hypertrophy

Background: Cardiac hypertrophy (CH) is the asymptomatic enlargement of ventricular walls witnessed in diabetes and hypertension, for which early metabolite differences and prediction are less stated previously. Aim: The aim of the study was (i) to understand the metabolic and ventricular events in diabetes and nondiabetes induced CH at the end of 2 weeks and (ii) to identify significant metabolite predictors and pathways that influence the seven metabolic and physiological responders of CH, namely, 3-hydroxybutyrate (3-HB); lactic acid; urea; and electrocardiography (ECG) waves (QRS complex, R amplitude, R-R interval, and heart rate). Methods: Diabetic rat models of CH using streptozotocin (40 mg/kg, i. p., single dose), and nondiabetic models using adrenaline (0.3 mg/kg, i. p, 2 weeks) were developed. Blood glucose levels, ECG, heart weight/body weight ratio, histopathological analysis, and serum metabolite analysis using gas chromatography mass spectrometry were performed at the end of 2 weeks. Strong metabolite predictors and pathways were identified using Pearson's correlation, multiple regression (MRA) and metabolite set enrichment (MSEA) analyses. Results: The prevalence of CH was observed through preliminary screenings at the end of 2 weeks. Galactose, leucine, erythrose, sorbitol, and valine were identified as significant ( P < 0.05) predictors in SZ model, whereas isoleucine, galactose, leucine, inositol, and palmitic acid were identified in ADR model. However, galactose metabolism, branched-chain amino acid, and lactose degradation pathways were mapped as the highly influential apparent pathways during early CH remodeling in both the models. Conclusion: This study identified putative initial metabolite shifts, significant predictors pathways that can aid in forecasting, intervention, and prevention of CH.