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Lookup NU author(s): Dr Elisa Villalobos Villegas, Dr Rachael RedgraveORCiD, James Clark, Dr Guy MacGowanORCiD, Professor Gavin RichardsonORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Introduction Adipocyte-like cells have been reported in the heart across multiple forms of cardiomyopathy, including ischaemic and non-ischaemic disease. However, their cellular origins and regulatory mechanisms remain poorly understood. Our work and others have identified fibro/adipogenic progenitors (FAPs) as key regulators of adipogenic plasticity in skeletal muscle, raising the possibility that related stromal populations in the heart may contribute to pathological lipid accumulation under disease conditions. Biomechanical cues, which differ markedly between ischaemic and non-ischaemic cardiomyopathy, may play a significant role in regulating this process. Here, we explored adipogenic features of stromal cell populations under biomechanical and pathological contexts relevant to ischaemic and non-ischaemic cardiomyopathy.Methods and Results Primary cardiac fibroblasts cultured on substrates of defined stiffness displayed lipid droplet accumulation evidenced by BODIPY staining. This was accompanied by modulation of fibrotic marker expression (Fibronectin, Collagen I and a-SMA) assessed by western blot (WB), indicating stiffness-dependent plasticity. In parallel, FAPs isolated from skeletal muscle demonstrated enhanced adipogenic potential on stiffer substrates evidenced by upregulation of protein levels of FABP4 (Fatty acid binding protein 4) by WB, supporting a role for biomechanical regulation of stromal cell fate. In contrast, FAPs from muscle of patients with Duchenne Muscular Dystrophy (DMD) displayed enhanced adipogenic differentiation on both soft and stiff substrates, suggesting a greater adipogenic capacity. To assess relevance in ischaemic cardiomyopathy, we evaluated markers of adipogenesis in mice subjected to myocardial infarction. Histological analysis of cardiac tissue revealed Perilipin 1 positive cells enriched in the infarct (border zone), suggesting adipogenic activity in this region.Conclusions Together, our preliminary findings suggest that biomechanical regulation of stromal cell plasticity may contribute to adipogenic features observed across cardiomyopathic states. Ongoing and future studies will extend this work to non-ischaemic cardiomyopathies, including DMD cardiac involvement, to define shared and context-specific mechanisms governing pathological adipogenesis in the heart.
Author(s): Villalobos E, Redgrave R, Clark J, MacGowan G, Richardson GD
Publication type: Article
Publication status: Published
Journal: Heart
Year: 2026
Volume: 112
Issue: Suppl 1
Print publication date: 09/06/2026
Online publication date: 09/06/2026
Acceptance date: 01/05/2026
Date deposited: 01/07/2026
ISSN (print): 1355-6037
ISSN (electronic): 1468-201X
Publisher: BMJ Group
URL: https://doi.org/10.1136/heartjnl-2026-BCS.326
DOI: 10.1136/heartjnl-2026-BCS.326
ePrints DOI: 10.57711/sdge-3553
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