Obesogenic diet leads to luminal overproduction of the complex IV inhibitor H 2 S and mitochondrial dysfunction in mouse colonocytes - Université de Rennes Accéder directement au contenu
Article Dans Une Revue FASEB Journal Année : 2023

Obesogenic diet leads to luminal overproduction of the complex IV inhibitor H 2 S and mitochondrial dysfunction in mouse colonocytes

Thomas Guerbette
Vincent Ciesielski
Olivier Loréal
Vincent Rioux
Gaëlle Boudry

Résumé

Obesity is characterized by systemic low-grade inflammation associated with disturbances of intestinal homeostasis and microbiota dysbiosis. Mitochondrial metabolism sustains epithelial homeostasis by providing energy to colonic epithelial cells (CEC) but can be altered by dietary modulations of the luminal environment. Our study aimed at evaluating whether the consumption of an obesogenic diet alters the mitochondrial function of CEC in mice. Mice were fed for 22 weeks with a 58% kcal fat diet (diet-induced obesity [DIO] group) or a 10% kcal fat diet (control diet, CTRL). Colonic crypts were isolated to assess mitochondrial function while colonic content was collected to characterize microbiota and metabolites. DIO mice developed obesity, intestinal hyperpermeability, and increased endotoxemia. Analysis of isolated colonic crypt bioenergetics revealed a mitochondrial dysfunction marked by decreased basal and maximal respirations and lower respiration linked to ATP production in DIO mice. Yet, CEC gene expression of mitochondrial respiration chain complexes and mitochondrial dynamics were not altered in DIO mice. In parallel, DIO mice displayed increased colonic bile acid concentrations, associated with higher abundance of Desulfovibrionaceae. Sulfide concentration was markedly increased in the colon content of DIO mice. Hence, chronic treatment of CTRL mouse colon organoids with sodium sulfide provoked mitochondrial dysfunction similar to that observed in vivo in DIO mice while acute exposure of isolated mitochondria from CEC of CTRL mice to sodium sulfide diminished complex IV activity. Our study provides new insights into colon mitochondrial dysfunction in obesity by revealing that increased sulfide production by DIO-induced dysbiosis impairs complex IV activity in mouse CEC.
Fichier principal
Vignette du fichier
Guerbette - Obesogenic diet leads to luminal overproduction of the complex IV inhibitor H2S and.pdf (2.27 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Licence : CC BY NC ND - Paternité - Pas d'utilisation commerciale - Pas de modification

Dates et versions

hal-04055777 , version 1 (07-04-2023)

Licence

Paternité - Pas d'utilisation commerciale - Pas de modification

Identifiants

Citer

Thomas Guerbette, Martin Beaumont, Mireille Andriamihaja, Vincent Ciesielski, Jean‐baptiste Perrin, et al.. Obesogenic diet leads to luminal overproduction of the complex IV inhibitor H 2 S and mitochondrial dysfunction in mouse colonocytes. FASEB Journal, 2023, 37 (4), pp.e22853. ⟨10.1096/fj.202201971R⟩. ⟨hal-04055777⟩
169 Consultations
26 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More