{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:14:23Z","timestamp":1792066463584,"version":"4.4.0"},"reference-count":49,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T00:00:00Z","timestamp":1731456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Regional Development Fund (ERDF) Integrated Territorial Initiative","award":["ITI0017_2019"],"award-info":[{"award-number":["ITI0017_2019"]}]},{"name":"European Regional Development Fund (ERDF) Integrated Territorial Initiative","award":["2020-019"],"award-info":[{"award-number":["2020-019"]}]},{"name":"Foundation Progreso y Salud PEER","award":["ITI0017_2019"],"award-info":[{"award-number":["ITI0017_2019"]}]},{"name":"Foundation Progreso y Salud PEER","award":["2020-019"],"award-info":[{"award-number":["2020-019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Excess lipid accumulation in the heart is associated with lipotoxicity and cardiac dysfunction due to excessive fatty acid oxidation. Peroxisome proliferator-activated receptor gamma (PPAR\u03b3) modulates the expression of key molecules involved in the FA metabolic pathway. Cardiomyocyte-specific overexpression of PPAR\u03b3 causes dilated cardiomyopathy associated with lipotoxicity in mice. miR-130b-3p has been shown to be downregulated in the plasma of idiopathic dilated cardiomyopathy patients, but its role in modulating cardiomyocyte lipotoxicity via PPAR\u03b3 remains unclear. Our objective was to investigate the protective role of miR-130b-3p against palmitate-induced lipotoxicity in cardiomyocytes through the modulation of the PPAR\u03b3 signaling pathway. Human cardiomyoblasts were treated with palmitate. Intracellular lipid accumulation and expression of PPAR\u03b3 and its downstream targets (CD36, FABP3, CAV1, VLDLR) were analyzed. Mitochondrial oxidative stress was assessed via MitoTracker Green and Redox Sensor Red staining and expression of CPT1B and SOD2. Endoplasmic reticulum stress and apoptosis were determined by examining GRP78, ATF6, XBP1s, CHOP, and caspase-3 expression. miR-130b-3p overexpression was achieved using transfection methods, and its effect on these parameters was evaluated. Luciferase assays were used to confirm PPAR\u03b3 as a direct target of miR-130b-3p. Palmitate treatment led to increased lipid accumulation and upregulation of PPAR\u03b3 and its downstream targets in human cardiomyoblasts. Palmitate also increased mitochondrial oxidative stress, endoplasmic reticulum stress and apoptosis. miR-130b-3p overexpression reduced PPAR\u03b3 expression and its downstream signaling, alleviated mitochondrial oxidative stress and decreased endoplasmic reticulum stress and apoptosis in palmitate-stimulated cardiomyoblasts. Luciferase assays confirmed PPAR\u03b3 as a direct target of miR-130b-3p. Our findings suggest that miR-130b-3p plays a protective role against palmitate-induced lipotoxicity in cardiomyocytes by modulating the PPAR\u03b3 signaling pathway.<\/jats:p>","DOI":"10.3390\/ijms252212161","type":"journal-article","created":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T06:10:48Z","timestamp":1731478248000},"page":"12161","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Protective Role of miR-130b-3p Against Palmitate-Induced Lipotoxicity in Cardiomyocytes Through PPAR\u03b3 Pathway"],"prefix":"10.3390","volume":"25","author":[{"given":"Elena","family":"Alonso-Villa","sequence":"first","affiliation":[{"name":"Biomedical Research and Innovation Institute of Cadiz (INiBICA), Research Unit, Puerta del Mar University Hospital, 11009 C\u00e1diz, Spain"},{"name":"Medicine Department, School of Medicine, University of Cadiz, 11002 C\u00e1diz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alipio","family":"Mangas","sequence":"additional","affiliation":[{"name":"Biomedical Research and Innovation Institute of Cadiz (INiBICA), Research Unit, Puerta del Mar University Hospital, 11009 C\u00e1diz, Spain"},{"name":"Medicine Department, School of Medicine, University of Cadiz, 11002 C\u00e1diz, Spain"},{"name":"Lipid and Atherosclerotic Unit, Internal Medicine Department, Puerta del Mar University Hospital Cardiology Service, 11009 C\u00e1diz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9855-8173","authenticated-orcid":false,"given":"Fernando","family":"Bonet","sequence":"additional","affiliation":[{"name":"Biomedical Research and Innovation Institute of Cadiz (INiBICA), Research Unit, Puerta del Mar University Hospital, 11009 C\u00e1diz, Spain"},{"name":"Medicine Department, School of Medicine, University of Cadiz, 11002 C\u00e1diz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d3scar","family":"Campuzano","sequence":"additional","affiliation":[{"name":"Hospital Josep Trueta, University of Girona, 17007 Girona, Spain"},{"name":"Cardiovascular Genetics Center, University of Girona-IDIBGI, 17190 Girona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red, Fisiopatolog\u00eda Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maribel","family":"Quezada-Feijoo","sequence":"additional","affiliation":[{"name":"Cardiology Department, Hospital Central de la Cruz Roja, 28003 Madrid, Spain"},{"name":"Medicine School, Alfonso X el Sabio University (UAX), 28691 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7654-6152","authenticated-orcid":false,"given":"M\u00f3nica","family":"Ramos","sequence":"additional","affiliation":[{"name":"Cardiology Department, Hospital Central de la Cruz Roja, 28003 Madrid, Spain"},{"name":"Medicine School, Alfonso X el Sabio University (UAX), 28691 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Garc\u00eda-Padilla","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Group, Department of Experimental Biology, University of Jaen, 23071 Jaen, Spain"},{"name":"Medina Foundation, Technology Park of Health Sciences, 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5669-7164","authenticated-orcid":false,"given":"Diego","family":"Franco","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Group, Department of Experimental Biology, University of Jaen, 23071 Jaen, Spain"},{"name":"Medina Foundation, Technology Park of Health Sciences, 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3136-1776","authenticated-orcid":false,"given":"Rocio","family":"Toro","sequence":"additional","affiliation":[{"name":"Biomedical Research and Innovation Institute of Cadiz (INiBICA), Research Unit, Puerta del Mar University Hospital, 11009 C\u00e1diz, Spain"},{"name":"Medicine Department, School of Medicine, University of Cadiz, 11002 C\u00e1diz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0188-4409(03)00004-3","article-title":"Heart Metabolic Disturbances in Cardiovascular Diseases","volume":"34","author":"Carvajal","year":"2003","journal-title":"Arch. 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