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Identification of metabolite shifts and early serum predictors for indicators of remodelling in diabetes and nondiabetic models of cardiac hypertrophy

 Department of Biochemistry, PSG College of Arts and Science, Coimbatore, Tamil Nadu, India

Correspondence Address:
Victor Arokia Doss,
Department of Biochemistry, PSG College of Arts and Science, Coimbatore - 641 014, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jmedsci.jmedsci_323_21

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.


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