The fasting-feeding metabolic transition regulates mitochondrial dynamics

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dc.contributor.authorCastro-Sepulveda, Mauricio
dc.contributor.authorMorio, Beatrice
dc.contributor.authorTunon-Suarez, Mauro
dc.contributor.authorJannas-Vela, Sebastian
dc.contributor.authorDiaz-Castro, Francisco
dc.contributor.authorRieusset, Jennifer
dc.contributor.authorZbinden-Foncea, Hermann
dc.date.accessioned2025-01-20T22:07:25Z
dc.date.available2025-01-20T22:07:25Z
dc.date.issued2021
dc.description.abstractIn humans, insulin resistance has been linked to an impaired metabolic transition from fasting to feeding (metabolic flexibility; MetFlex). Previous studies suggest that mitochondrial dynamics response is a putative determinant of MetFlex; however, this has not been studied in humans. Thus, the aim of this study was to investigate the mitochondrial dynamics response in the metabolic transition from fasting to feeding in human peripheral blood mononuclear cells (PBMCs). Six male subjects fasted for 16 h (fasting), immediately after which they consumed a 75-g oral glucose load (glucose). In both fasting and glucose conditions, blood samples were taken to obtain PBMCs. Mitochondrial dynamics were assessed by electron microscopy images. We exposed in vitro acetoacetate-treated PBMCs to the specific IP3R inhibitor Xestospongin B (XeB) to reduce IP3R-mediated mitochondrial Ca2+ accumulation. This allowed us to evaluate the role of ER-mitochondria Ca2+ exchange in the mitochondrial dynamic response to substrate availability. To determine whether PBMCs could be used in obesity context (low MetFlex), we measured mitochondrial dynamics in mouse spleen-derived lymphocytes from WT and ob/ob mice. We demonstrated that the transition from fasting to feeding reduces mitochondria-ER interactions, induces mitochondrial fission and reduces mitochondrial cristae density in human PBMCs. In addition, we demonstrated that IP3R activity is key in the mitochondrial dynamics response when PBMCs are treated with a fasting-substrate in vitro. In murine mononuclear-cells, we confirmed that mitochondria-ER interactions are regulated in the fasted-fed transition and we further highlight mitochondria-ER miscommunication in PBMCs of diabetic mice. In conclusion, our results demonstrate that the fasting/feeding transition reduces mitochondria-ER interactions, induces mitochondrial fission and reduces mitochondrial cristae density in human PBMCs, and that IP3R activity may potentially play a central role.
dc.fuente.origenWOS
dc.identifier.doi10.1096/fj.202100929R
dc.identifier.eissn1530-6860
dc.identifier.issn0892-6638
dc.identifier.urihttps://doi.org/10.1096/fj.202100929R
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/94239
dc.identifier.wosidWOS:000702238200066
dc.issue.numero10
dc.language.isoen
dc.revistaFaseb journal
dc.rightsacceso restringido
dc.subjectfasting
dc.subjectmitochondria-ER interaction
dc.subjectmitochondrial cristae
dc.subjectmitochondrial fusion
dc.subjectmitochondrial morphology
dc.subjectobesity
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleThe fasting-feeding metabolic transition regulates mitochondrial dynamics
dc.typeartículo
dc.volumen35
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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