2026-05-14T16:33:19Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/274472026-04-28T00:18:00Zcom_20.500.12105_19586com_20.500.12105_2202col_20.500.12105_19587

00925njm 22002777a 4500 dc Galán-Arriola, Carlos author Pérez-Camargo, Daniel author Ferrarini, Alessia author Mastrangelo, Annalaura author Higuero-Verdejo, María Isabel author López-Martín, Gonzalo Javier author Devesa, Ana author Gutiérrez, Rocío Villena author Fernández-Tocino, Miguel author Díaz-Guerra, Anabel author Montero-Cruces, Lourdes author Carnero, Manuel author Fernández-Jiménez, Rodrigo author Fuster, Valentin author Sánchez-González, Javier author Ibáñez, Borja author 2026-03-27 Most forms of heart failure are characterized by a metabolic switch from the use of fatty acids to glucose as the main fuel source for ATP generation in the myocardium. Whether metabolic reprogramming is a therapeutic target remains controversial. In this study, heart failure with reduced ejection fraction (HFrEF) and metabolic switch (i.e., increased myocardial glucose uptake) was induced in pigs by generating viable dysfunctional myocardium secondary to progressive coronary artery stenosis. Pigs (n = 19) were then randomized to a high-fat diet (HFD, chow diet supplemented with 20% lard) or control diet (no supplementation) for two months. Pre- and post-nutritional treatment contrast-enhanced cardiac magnetic resonance (CMR) and FDG-PET/CT studies were performed. Hearts were then harvested for further analysis. LVEF significantly improved in pigs receiving the 2-month HFD (38% [33, 43] to 54% [47, 62], p = 0.036) but remained unchanged in control-diet pigs (36% [35, 45] to 41% [38, 43], p = 0.24). HFD-fed pigs had a smaller extent of fibrosis after the dietary intervention (late gadolinium enhancement 0.45% LV [0.17, 1.67] vs 6.23 [5.54, 9.57], p = 0.0047). On FDG-PET, a reversion of the metabolic reprogramming in the LAD-dysfunctional myocardium was observed only in HFD-fed pigs (0.46 counts [0.21, 0.65] vs 1.80 [1.53, 2.83], p = 0.016). Transmission electron microscopy of explanted hearts revealed less fragmented mitochondrial and a lower lipid droplet density in cardiomyocytes from HFD-fed pigs (38 per 10 µm3 [34, 50] vs 96 [78, 124], p = 0.022), and this was accompanied by increased expression of genes involved in fatty acid metabolism and downregulation of genes encoding glucose import proteins. In conclusion, in a large animal model of HFrEF secondary to myocardial dysfunction with a metabolic switch, a nutritional intervention based on HFD feeding was associated with a cardiac metabolic restoration of fatty acid substrate use, restoration of cardiomyocyte lipid trafficking and significantly improved systolic function. Basic Res Cardiol. 2026 Mar 27. BASIC RESEARCH IN CARDIOLOGY 41894020 https://hdl.handle.net/20.500.12105/27447 Heart failure High-fat diet Magnetic resonance imaging Mitochondria A high-fat diet nutritional intervention reprograms cardiac metabolism and improves systolic function in a pig model of heart failure with reduced ejection fraction.