Mitofusin-2 induced by exercise modifies lipid droplet-mitochondria communication, promoting fatty acid oxidation in male mice with NAFLD

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dc.contributor.authorBorquez, Juan Carlos
dc.contributor.authorDiaz-Castro, Francisco
dc.contributor.authorPino-de La Fuente, Francisco
dc.contributor.authorEspinoza, Karla
dc.contributor.authorFigueroa, Ana Maria
dc.contributor.authorMartinez-Ruiz, Inma
dc.contributor.authorHernandez, Vanessa
dc.contributor.authorLopez-Soldado, Iliana
dc.contributor.authorVentura, Raill
dc.contributor.authorDomingo, Joan Carles
dc.contributor.authorBosch, Marta
dc.contributor.authorFajardo, Alba
dc.contributor.authorSebastian, David
dc.contributor.authorEspinosa, Alejandra
dc.contributor.authorPol, Albert
dc.contributor.authorZorzano, Antonio
dc.contributor.authorCortes, Victor
dc.contributor.authorHernandez-Alvarez, Maria Isabel
dc.contributor.authorTroncoso, Rodrigo
dc.date.accessioned2025-01-20T17:08:48Z
dc.date.available2025-01-20T17:08:48Z
dc.date.issued2024
dc.description.abstractBackground and aim: The excessive accumulation of lipid droplets (LDs) is a defining characteristic of nonalcoholic fatty liver disease (NAFLD). The interaction between LDs and mitochondria is functionally important for lipid metabolism homeostasis. Exercise improves NAFLD, but it is not known if it has an effect on hepatic LD-mitochondria interactions. Here, we investigated the influence of exercise on LD-mitochondria interactions and its significance in the context of NAFLD. Approach and results: Mice were fed high-fat diet (HFD) or HFD-0.1 % methionine and choline-deficient diet (MCD) to emulate simple hepatic steatosis or non-alcoholic steatohepatitis, respectively. In both models, aerobic exercise decreased the size of LDs bound to mitochondria and the number of LD-mitochondria contacts. Analysis showed that the effects of exercise on HOMA-IR and liver triglyceride levels were independent of changes in body weight, and a positive correlation was observed between the number of LD-mitochondria contacts and NAFLD severity and with the lipid droplet size bound to mitochondria. Cellular fractionation studies revealed that ATP -coupled respiration and fatty acid oxidation (FAO) were greater in hepatic peridroplet mitochondria (PDM) from HFD-fed exercised mice than from equivalent sedentary mice. Finally, exercise increased FAO and mitofusin-2 abundance exclusively in PDM through a mechanism involving the curvature of mitochondrial membranes and the abundance of saturated lipids. Accordingly, hepatic mitofusin-2 ablation prevented exercise-induced FAO in PDM. Conclusions: This study demonstrates that aerobic exercise has beneficial effects in murine NAFLD models by lessening the interactions between hepatic LDs and mitochondria, and by decreasing LD size, correlating with a reduced severity of NAFLD. Additionally, aerobic exercise increases FAO in PDM and this process is reliant on Mfn-2 enrichment, which modifies LD-mitochondria communication.
dc.fuente.origenWOS
dc.identifier.doi10.1016/j.metabol.2023.155765
dc.identifier.eissn1532-8600
dc.identifier.issn0026-0495
dc.identifier.urihttps://doi.org/10.1016/j.metabol.2023.155765
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/90985
dc.identifier.wosidWOS:001165870100001
dc.language.isoen
dc.revistaMetabolism-clinical and experimental
dc.rightsacceso restringido
dc.subjectSteatohepatitis
dc.subjectPeridroplet mitochondria
dc.subjectMitofusin-2
dc.subjectHepatocytes
dc.subjectFatty acid oxidation
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleMitofusin-2 induced by exercise modifies lipid droplet-mitochondria communication, promoting fatty acid oxidation in male mice with NAFLD
dc.typeartículo
dc.volumen152
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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