The fasting-feeding metabolic transition regulates mitochondrial dynamics

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dc.contributor.authorCastro-Sepulveda, Mauricio
dc.contributor.authorMorio, Béatrice
dc.contributor.authorTuñón-Suárez, Mauro
dc.contributor.authorJannas-Vela, Sebastian
dc.contributor.authorDíaz-Castro, Francisco
dc.contributor.authorRieusset, Jennifer
dc.contributor.authorZbinden-Foncea, Hermann
dc.date.accessioned2022-01-07T14:58:23Z
dc.date.available2022-01-07T14:58:23Z
dc.date.issued2021-10-10
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.es
dc.description.sponsorshipThis study was funded by Research Grant awarded to MCS by Universidad Finis Terrae (Grant no. CAI 2019). The work was further supported by Universidad Finis Terrae through projects grants awarded to HZFen
dc.identifier.citationThe FASEB Journal, Vol. 35, N°10, (2021) p. 1-12. en
dc.identifier.doihttps://doi.org/10.1096/fj.202100929R
dc.identifier.issn1530-6860
dc.identifier.orcidhttps://orcid.org/0000-0002-2270-299X
dc.identifier.urihttp://hdl.handle.net/20.500.12254/2224
dc.language.isoenen
dc.publisherFederation of American Society of Experimental Biology (FASEB)es
dc.rightsAtribución-NoComercial-CompartirIgual 3.0 Chile (CC BY-NC-SA 3.0 CL)
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/cl/
dc.subject.otherFastinges
dc.subject.otherObesityes
dc.subject.otherMitochondrial fusiones
dc.subject.otherMitochondrial cristaees
dc.subject.otherMitochondrial morphologyes
dc.subject.otherMitochondria-ER interactiones
dc.titleThe fasting-feeding metabolic transition regulates mitochondrial dynamicsen
dc.typeArtículoes
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