Qin SS, Wu ZM, Zheng BS, Luo C. Maladaptive lipid partitioning in obesity-related heart failure with preserved ejection fraction: From depot dysfunction to metabolic phenotyping. World J Cardiol 2026; 18(10): 125519 [DOI: 10.4330/wjc.125519]
Corresponding Author of This Article
Cheng Luo, MD, Postdoc, Assistant Professor, Department of Cardiovascular Surgery, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Qingxiu District, Nanning 530021, Guangxi Zhuang Autonomous Region, China. drluocheng@163.com
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Cardiac & Cardiovascular Systems
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review-article
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Qin SS, Wu ZM, Zheng BS, Luo C. Maladaptive lipid partitioning in obesity-related heart failure with preserved ejection fraction: From depot dysfunction to metabolic phenotyping. World J Cardiol 2026; 18(10): 125519 [DOI: 10.4330/wjc.125519]
World J Cardiol. Oct 26, 2026; 18(10): 125519 Published online Oct 26, 2026. doi: 10.4330/wjc.125519
Maladaptive lipid partitioning in obesity-related heart failure with preserved ejection fraction: From depot dysfunction to metabolic phenotyping
Si-Shang Qin, Zi-Min Wu, Bao-Shi Zheng, Cheng Luo
Si-Shang Qin, Zi-Min Wu, Bao-Shi Zheng, Cheng Luo, Department of Cardiovascular Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Co-first authors: Si-Shang Qin and Zi-Min Wu.
Co-corresponding authors: Bao-Shi Zheng and Cheng Luo.
Author contributions: Qin SS contributed to the review conceptualization and the manuscript drafting; Qin SS, Wu ZM, and Luo C contributed to the review and the revision of the manuscript; Luo C and Zheng BS contributed to the supervision of the work; Zheng BS contributed to the project administration and funding acquisition. Zheng BS and Luo C contributed equally to this work as co-corresponding authors. Qin SS and Wu ZM contributed equally to this work as co-first authors.
AI contribution statement: The authors declare that no AI tools were used in the development or writing of this manuscript and take full responsibility for its integrity, accuracy, and originality.
Supported by the Natural Science Foundation of Guangxi, No. 2025GXNSFAA069056; the National Natural Science Foundation of China, No. 82360066; and the Guangxi Key Research and Development Program Project, No. guikeAB24010153.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Cheng Luo, MD, Postdoc, Assistant Professor, Department of Cardiovascular Surgery, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Qingxiu District, Nanning 530021, Guangxi Zhuang Autonomous Region, China. drluocheng@163.com
Received: July 9, 2026 Revised: September 9, 2026 Accepted: October 13, 2026 Published online: October 26, 2026 Processing time: 106 Days and 12.9 Hours
Abstract
Heart failure with preserved ejection fraction is a heterogeneous syndrome, with obesity defining an increasingly treatable cardiometabolic phenotype. Building on recent work identifying dysfunctional adiposity as an upstream contributor, this minireview focuses on the complementary question of how failure of safe lipid storage redirects substrate across visceral, hepatic, skeletal muscle, epicardial, perivascular, and myocardial compartments, and how this depot-specific routing intersects with myocardial metabolic inflexibility. Human imaging, invasive physiology, myocardial metabolomics, and recent clinical trials support associations between ectopic adiposity, insulin resistance, inflammation, impaired vascular and atrial reserve, congestion, and exercise intolerance, although causal pathways remain incompletely established in humans. We therefore propose an adiposity-aware, hypothesis-generating framework integrating body composition, regional adipose depots, metabolic-inflammatory biomarkers, atrial and right-sided function, and exercise assessment for phenotype-enriched research and future trial design. This framework is not intended to guide current treatment selection. Established treatment should remain evidence based, including exercise, sodium-glucose cotransporter 2 inhibition, mineralocorticoid receptor antagonism, decongestion, and obesity-directed incretin therapy, with attention to lean-mass preservation. Future prospective studies should investigate whether depot quality, metabolic flexibility, sex and ethnic heterogeneity, and body composition provide additional information for phenotypic characterization and risk stratification beyond conventional measures.
Core Tip: Obesity-related heart failure with preserved ejection fraction cannot be adequately characterized by body mass alone. This minireview focuses on the less frequently explored consequences of failed lipid storage: Depot-specific lipid rerouting across visceral, hepatic, skeletal muscle, epicardial/perivascular, and myocardial compartments, together with impaired myocardial substrate flexibility. We distinguish human associations from mechanistic evidence and propose adiposity-aware phenotyping as a research framework rather than a validated treatment algorithm. Recent cardiometabolic trials illustrate how complementary components of this phenotype may be therapeutically modifiable.
