Quercetin alleviates obesity-related cardiomyopathy via dual modulation of Fabp3 and Adipoq: a proteomics-based mechanistic study

Obesity-related cardiomyopathy involves metabolic dysregulation, oxidative stress, fibrosis and cardiac dysfunction. We investigated quercetin using tandem mass tag-based cardiac proteomics in high-fat diet (HFD)-fed mice. We identified 180 differentially expressed proteins (DEPs) between HFD and control mice and 303 between quercetin-treated and untreated HFD mice. Pathway analyses implicated lipid metabolism, peroxisome proliferator-activated receptor (PPAR) signalling and branched-chain amino acid degradation. Among 36 overlapping DEPs, 35 exhibited opposite changes across comparisons, highlighting heart-type fatty acid-binding protein 3 (Fabp3) and adiponectin (Adipoq) as candidate response-associated proteins. Western blotting confirmed elevated myocardial Fabp3 and reduced Adipoq with HFD, both shifted toward control levels following quercetin treatment, alongside restored AMP-activated protein kinase (AMPK) phosphorylation and reduced PPARα expression. Qualitative Oil Red O staining showed no overt myocardial neutral-lipid accumulation despite increased hepatic lipid staining in HFD mice. Molecular docking predicted favourable binding poses for quercetin with Fabp3 and Adipoq (− 8.8 and − 8.2 kcal/mol), without establishing direct binding. Quercetin also attenuated oxidative stress, inflammation, collagen deposition and cardiac dysfunction. These findings suggest coordinated Fabp3-, Adipoq-, AMPK- and PPARα-associated responses, warranting causal validation.