Catestatin restores cardiac metabolic flexibility and enhances mitochondrial function

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.

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Publication Details

Journal
Communications Biology
Published
2026-05-23
DOI
https://doi.org/10.1038/s42003-026-10310-z
Primary Topic
Renin-Angiotensin System Studies
Type
article
Field-Weighted Citation Impact
0.00

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article

Catestatin restores cardiac metabolic flexibility and enhances mitochondrial function

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Communications Biology
Renin-Angiotensin System Studies
article

Catestatin restores cardiac metabolic flexibility and enhances mitochondrial function

Sumana Mahata, Teresa Pasqua, Sanjib Senapati, Geert van den Bogaart, Satadeepa Kal, Suborno Jati, Ennio Avolio, Brian Head, Debashis Sahoo, Shrabastee Chakraborty, Nilima Biswas, Kechun Tang, Sushil K. Mahata, Hemal H. Patel, Venkat R. Chirasani, Gautam Bandyopadhyay, Ramamurthy Chitteti
article en

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.

Communications Biology
University of North Carolina at Chapel Hill (US), University of Groningen (NL), Indian Institute of Technology Madras (IN), University of Michigan (US), UC San Diego Health System (US), University Health System (US), University of California San Diego (US), Magna Graecia University (IT), VA San Diego Healthcare System (US), Veterans Medical Research Foundation of San Diego (US), University of Calabria (IT)
U.S. Department of Defense, U.S. Department of Veterans Affairs, National Institutes of Health
Affordable and clean energy, Good health and well-being
Openalex Percentile: Top 5%
Renin-Angiotensin System Studies
DOIOpen Access PDFOpenAlex
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