Year: 2026
Type: article
Abstract: Diabetic cardiomyopathy (DbCM) is an important contributor to heart failure (HF) in diabetes, occurring independently of other cardiovascular risk factors. Accumulating evidence demonstrates that cardiac lipotoxicity is a key driver of the onset and progression of DbCM and HF. Myocardial lipid homeostasis is coordinated by multiple transcriptional regulations, signaling pathway activation, and endoplasmic reticulum-mediated management involved in lipid metabolism. In DbCM, unbalanced fatty acid (FA) influx, handling, storage, and utilization initiates lipid overload, accumulation of toxic lipid intermediates (e.g., diacylglycerols and ceramides), and activation of maladaptive response. Notably, these lipid intermediates amplify reactive oxygen species (ROS) generation, which serves as a critical link between lipotoxic signaling and mitochondrial dysfunction by promoting electron leak, mitochondrial damage, and activation of inflammatory and cell-death pathways. These processes converge on adverse remodeling and contractile impairment, accelerating DbCM progression. This review integrates mechanistic and translational evidence linking dysregulated lipid handling to DbCM and discusses the potential therapeutic strategies that target lipid abnormalities.
DOI: 10.3390/ijms27062740
Authors: Yihua Han, Xinyi Chen, Oveena Fonseka, Wei Liu
Institution: University of Manchester
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,499
Funder: British Heart Foundation
Awards: An investigation into the molecular basis and impacts of cardiac FGF21 resistance in response to metabolic stress, Investigate a novel regulation of cardiac lipid homeostasis in metabolic disorder, Does modulation of cardiac HMGB1 prevent myocardial inflammation in diabetes?, Ability of FGFR1/KLB to prevent cardiac microvascular impairment and pathological remodelling in response to metabolic stress
OpenAlex ID: W7138059031