Catestatin restores cardiac metabolic flexibility and enhances mitochondrial function
Year: 2026
Type: article
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.
Source: Communications Biology
Authors: Satadeepa Kal, Venkat R. Chirasani, Nilima Biswas, Sumana Mahata, Sumana Mahata, Suborno Jati, Kechun Tang, Teresa Pasqua, Ennio Avolio, Ramamurthy Chitteti, Shrabastee Chakraborty, Gautam Bandyopadhyay, Brian P. Head, Geert van den Bogaart, Hemal H. Patel, Debashis Sahoo, Sanjib Senapati, Sushil K. Mahata, Sushil K. Mahata
Institutions: University of California San Diego, Veterans Medical Research Foundation of San Diego, University of North Carolina at Chapel Hill, Indian Institute of Technology Madras, VA San Diego Healthcare System, Magna Graecia University, University of Calabria, University of Michigan, University of Groningen
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,190
Awards: G196021734, Macrophage Polarization in Response to Infections and Inflammation, Chromogranin A is an aging risk factor, Peptide therapy for age-associated gut dysmotility, G6316358227, G687391183, Annotation of cell types in human colon tissue using Boolean analysis, Network-Based Novel Therapeutics in Colorectal Cancers, Precision therapeutics of inflammatory bowel disease guided by Boolean logic, G9000050198, G9000189195
OpenAlex ID: W7162215246