Pomegranate peel extract counteracts palmitate-induced insulin resistance by inducing mitophagy, reducing inflammation, and regulating MAPK signaling in C2C12 myotubes

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dc.article.number107433
dc.catalogadoraba
dc.contributor.authorBustamante, Andrés
dc.contributor.authorGutiérrez, Juan
dc.contributor.authorChávez, Vilma
dc.contributor.authorLemus, Roberto
dc.contributor.authorMuñoz Medina, Cristóbal
dc.contributor.authorCarriel Nesvara, Alfonso
dc.contributor.authorLeón, Emilson
dc.contributor.authorFredes González, Carolina Paz
dc.contributor.authorAguirre Polanco, Carolina
dc.contributor.authorParada Daza, Alejandra
dc.contributor.authorCastro Sepúlveda, Mauricio
dc.contributor.authorEcheverría González, Francisca
dc.date.accessioned2025-08-29T15:47:59Z
dc.date.available2025-08-29T15:47:59Z
dc.date.issued2025
dc.description.abstractPomegranate peel, a by-product rich in ellagitannin-type polyphenols, was dried at 60 °C and extracted (ethanol:water, 38:62 v/v) to yield an extract characterized for total polyphenols, punicalagin, ellagic acid (Folin–Ciocalteu assay and HPLC), and antioxidant capacity (DPPH, FRAP, ORAC). To assess its protective effects against insulin resistance induced by palmitic acid, differentiated C2C12 skeletal muscle myotubes were treated for 6 h with vehicle (0.25 % bovine serum albumin), palmitic acid (0.2 mM), or palmitic acid plus pomegranate peel extract (equivalent to 100 μM punicalagin). Insulin signaling (p-AKTSer473), mechanistic target of rapamycin pathway activity, mitogen-activated protein kinase signaling, and NF-κB activation (IκBαSer32) were quantified by Western blotting; autophagic flux was assessed via the LC3 II/I ratio; mitochondrial morphology by transmission electron microscopy; and mitochondrial reactive oxygen species by MitoSOX™ flow cytometry. Data were analyzed by one-way ANOVA and Tukey's test or Friedman test with Dunn's post hoc (p < 0.05), according to data distribution. Compared to palmitic acid alone, pomegranate peel extract fully restored insulin-stimulated AKT phosphorylation, attenuated mitochondrial reactive oxygen species accumulation, increased the LC3 II/I ratio, induced mitophagosome formation and mitochondrial elongation, and modulated MAPK activation. In conclusion, pomegranate peel extract prevented palmitate-induced insulin resistance in muscle cells by activating mitophagy and rebalancing key signaling pathways, highlighting its potential as a functional ingredient to enhance muscle insulin sensitivity and mitochondrial health.
dc.description.funderPontificia Universidad Católica de Chile; Folios: V CONCURSO DE APOYO A LA INVESTIGACIÓN 2022-DEPARTAMENTO DE CIENCIAS DE LA SALUD (DCS) - PLANTA ORDINARIA, VRI-INICIO-2024-6
dc.description.funderANID/FONDECYT; Folios: 11180736, 11230548
dc.format.extent11 páginas
dc.fuente.origenORCID
dc.identifier.doi10.1016/j.fbio.2025.107433
dc.identifier.eissn2212-4306
dc.identifier.issn2212-4292
dc.identifier.scopusid105013654794
dc.identifier.urihttps://doi.org/10.1016/j.fbio.2025.107433
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/105370
dc.information.autorucDepartamento de Ciencias de la Salud; Fredes González, Carolina Paz; S/I; 143943
dc.information.autorucEscuela de Medicina; Aguirre Polanco, Carolina; 0000-0002-5573-9000; 1012275
dc.information.autorucDepartamento de Ciencias de la Salud; Parada Daza, Alejandra; S/I; 127953
dc.information.autorucDepartamento de Ciencias de la Salud; Echeverría González, Francisca; 0000-0002-9661-0377; 1232657
dc.language.isoen
dc.nota.accesocontenido parcial
dc.revistaFood Bioscience
dc.rightsacceso restringido
dc.subjectAgro-industrial by-products
dc.subjectFunctional foods
dc.subjectEllagitannins
dc.subjectSkeletal muscle
dc.subjectOxidative stress
dc.subjectMitochondrial dynamics
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titlePomegranate peel extract counteracts palmitate-induced insulin resistance by inducing mitophagy, reducing inflammation, and regulating MAPK signaling in C2C12 myotubes
dc.typeartículo
sipa.codpersvinculados143943
sipa.codpersvinculados1012275
sipa.codpersvinculados127953
sipa.codpersvinculados1232657
sipa.indexSCOPUS
sipa.trazabilidadORCID;2025-08-22
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