Palmitic acid control of ciliogenesis modulates insulin signaling in hypothalamic neurons through an autophagy-dependent mechanism

Simple item page
dc.contributor.authorAvalos, Yenniffer
dc.contributor.authorPaz Hernandez-Caceres, Maria
dc.contributor.authorLagos, Pablo
dc.contributor.authorPinto-Nunez, Daniela
dc.contributor.authorRivera, Patricia
dc.contributor.authorBurgos, Paulina
dc.contributor.authorDiaz-Castro, Francisco
dc.contributor.authorJoy-Immediato, Michelle
dc.contributor.authorVenegas-Zamora, Leslye
dc.contributor.authorLopez-Gallardo, Erik
dc.contributor.authorKretschmar, Catalina
dc.contributor.authorBatista-Gonzalez, Ana
dc.contributor.authorCifuentes-Araneda, Flavia
dc.contributor.authorToledo-Valenzuela, Lilian
dc.contributor.authorRodriguez-Pena, Marcelo
dc.contributor.authorEspinoza-Caicedo, Jasson
dc.contributor.authorPerez-Leighton, Claudio
dc.contributor.authorBertocchi, Cristina
dc.contributor.authorCerda, Mauricio
dc.contributor.authorTroncoso, Rodrigo
dc.contributor.authorParra, Valentina
dc.contributor.authorBudini, Mauricio
dc.contributor.authorBurgos, Patricia, V
dc.contributor.authorCriollo, Alfredo
dc.contributor.authorMorselli, Eugenia
dc.date.accessioned2024-01-10T12:37:15Z
dc.date.available2024-01-10T12:37:15Z
dc.date.issued2022
dc.description.abstractPalmitic acid (PA) is significantly increased in the hypothalamus of mice, when fed chronically with a high-fat diet (HFD). PA impairs insulin signaling in hypothalamic neurons, by a mechanism dependent on autophagy, a process of lysosomal-mediated degradation of cytoplasmic material. In addition, previous work shows a crosstalk between autophagy and the primary cilium (hereafter cilium), an antenna-like structure on the cell surface that acts as a signaling platform for the cell. Ciliopathies, human diseases characterized by cilia dysfunction, manifest, type 2 diabetes, among other features, suggesting a role of the cilium in insulin signaling. Cilium depletion in hypothalamic pro-opiomelanocortin (POMC) neurons triggers obesity and insulin resistance in mice, the same phenotype as mice deficient in autophagy in POMC neurons. Here we investigated the effect of chronic consumption of HFD on cilia; and our results indicate that chronic feeding with HFD reduces the percentage of cilia in hypothalamic POMC neurons. This effect may be due to an increased amount of PA, as treatment with this saturated fatty acid in vitro reduces the percentage of ciliated cells and cilia length in hypothalamic neurons. Importantly, the same effect of cilia depletion was obtained following chemical and genetic inhibition of autophagy, indicating autophagy is required for ciliogenesis. We further demonstrate a role for the cilium in insulin sensitivity, as cilium loss in hypothalamic neuronal cells disrupts insulin signaling and insulin-dependent glucose uptake, an effect that correlates with the ciliary localization of the insulin receptor (IR). Consistently, increased percentage of ciliated hypothalamic neuronal cells promotes insulin signaling, even when cells are exposed to PA. Altogether, our results indicate that, in hypothalamic neurons, impairment of autophagy, either by PA exposure, chemical or genetic manipulation, cause cilia loss that impairs insulin sensitivity.
dc.fechaingreso.objetodigital2024-04-25
dc.fuente.origenWOS
dc.identifier.doi10.1038/s41419-022-05109-9
dc.identifier.issn2041-4889
dc.identifier.urihttps://doi.org/10.1038/s41419-022-05109-9
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/76797
dc.identifier.wosidWOS:000832912800002
dc.information.autorucFacultad de Ciencias Biológicas; Bertocchi No Informado, Cristina; S/I; 1078032
dc.issue.numero7
dc.language.isoen
dc.nota.accesocontenido completo
dc.publisherSPRINGERNATURE
dc.revistaCELL DEATH & DISEASE
dc.rightsacceso abierto
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titlePalmitic acid control of ciliogenesis modulates insulin signaling in hypothalamic neurons through an autophagy-dependent mechanism
dc.typeartículo
dc.volumen13
sipa.codpersvinculados1078032
sipa.indexWOS
sipa.trazabilidadCarga SIPA;09-01-2024
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Palmitic acid control of ciliogenesis modulates insulin signaling in hypothalamic neurons through an autophagy-dependent mechanism.pdf
Size:
4.81 MB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Artículos de revistas