Catestatin supplementation in CST-knockout mice restored cardiac metabolic flexibility by increasing glucose uptake 2.9-fold and enhancing mitochondrial ATP production.
Does catestatin improve cardiac metabolic flexibility and mitochondrial function in models of hypertension-associated heart failure?
Catestatin acts as a key regulator of cardiac energy metabolism, revealing an endocrine-mitochondrial signaling axis with therapeutic potential for hypertension-associated heart failure.
Abstract Hypertension is a major risk factor for heart failure, characterized by impaired energy metabolism and mitochondrial dysfunction. The endogenous peptide catestatin (CST) has known cardiovascular protective effects, but its role in cardiac metabolism remains unclear. Here, we show that CST regulates cardiac metabolic pathways through integrated transcriptomic and network analyses, identifying cell-type-specific gene programs that are disrupted in its absence and restored with supplementation. Comparative analysis with human heart failure datasets reveals conserved alterations in glucose and fatty acid metabolism and mitochondrial function. Functional studies demonstrate that CST restores metabolic flexibility by shifting substrate utilization toward glucose oxidation. Mechanistically, CST enhances mitochondrial ATP production by interacting with ATP synthase and improving membrane potential and enzyme activity. These findings establish CST as a key regulator of cardiac energy metabolism and reveal an endocrine–mitochondrial signaling axis with therapeutic potential for hypertension-associated heart failure.
May 23, 2026 publication; aligns with recent mitochondrial research buzz in cardiology.
Kal et al. (Sat,) conducted a other in Hypertension-associated heart failure and metabolic dysfunction. Catestatin (CST) vs. Saline or Wild-type (WT) controls was evaluated on Glucose uptake and mitochondrial function. Catestatin supplementation in CST-knockout mice restored cardiac metabolic flexibility by increasing glucose uptake 2.9-fold and enhancing mitochondrial ATP production.