The fasting-feeding metabolic transition regulates mitochondrial dynamics

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 HZFes
dc.identifier.citationCastro-Sepúlveda M, Morio B, Tuñón-Suárez M, et al. The fastingfeeding metabolic transition regulates mitochondrial dynamics. FASEB J. 2021;35:e21891. https://doi.org/10.1096/fj.202100929Res
dc.identifier.issn1530-6860
dc.identifier.orcidhttps://doi.org/10.1096/fj.202100929R
dc.identifier.urihttp://hdl.handle.net/20.500.12254/2224
dc.language.isoenes
dc.publisherFederation of American Society of Experimental Biology (FASEB)es
dc.relation.ispartofseriesFASEB Journal;
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.otherMitochondria-ER interactiones
dc.subject.otherMitochondrial cristaees
dc.subject.otherMitochondrial fusiones
dc.subject.otherMitochondrial morphologyes
dc.subject.otherObesityes
dc.titleThe fasting-feeding metabolic transition regulates mitochondrial dynamicses
dc.typeArtículoes
Files
Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
The fasting-feeding metabolic transition regulates mitochondrial dynamics-2-13.pdf
Size:
2.85 MB
Format:
Adobe Portable Document Format
Description:
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
638 B
Format:
Item-specific license agreed upon to submission
Description: