{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:31:23Z","timestamp":1760059883996,"version":"build-2065373602"},"reference-count":47,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T00:00:00Z","timestamp":1752710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"EUR CARe","award":["N\u00b0ANR-18-EURE-0003","N\u00b0ANR-18-EURE-0003","N\u00b08-2023"],"award-info":[{"award-number":["N\u00b0ANR-18-EURE-0003","N\u00b0ANR-18-EURE-0003","N\u00b08-2023"]}]},{"name":"INSPIRE and the European Regional Development Fund","award":["N\u00b0ANR-18-EURE-0003","N\u00b0ANR-18-EURE-0003","N\u00b08-2023"],"award-info":[{"award-number":["N\u00b0ANR-18-EURE-0003","N\u00b0ANR-18-EURE-0003","N\u00b08-2023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>A high-fat diet (HFD) has significant effects on health, leading to cardiovascular, metabolic, neurodegenerative, and psychiatric conditions and contributing to obesity and type 2 diabetes. Mitochondria, essential for energy production and oxidative metabolism, are adversely affected by a HFD, causing oxidative stress and impaired cellular function. Mutations in the OPA1 (OPtic Atrophy 1) gene, crucial for mitochondrial dynamics and functions, are responsible for dominant optic atrophy (DOA), a mitochondrial neurodegenerative disease associated with increased reactive oxygen species (ROS). The expressivity of DOA is highly variable, even within the same family. This suggests that both modifying genetics and environmental factors could influence the penetrance of the disease. We previously demonstrated that genetic background modulates DOA expressivity and now ask if this is also the case for external cues. We thus explore how OPA1 deficiency interacts with HFD-induced metabolic disturbances, hypothesizing that long-term HFD consumption impairs brain mitochondrial function and disrupts oxidative metabolism. OPA1+\/\u2212 mice were thus subjected to a HFD for a period of 12 weeks, and ROS levels and the expression of antioxidant genes were evaluated by Western blot and spectrophotometry. Cortices from high-fat diet-fed OPA1+\/\u2212 mice showed lower aconitase activity than those of their wild-type (WT) litter mates, indicative of an unbalanced increase in mitochondrial ROS. Accordingly, OPA1+\/\u2212 mice present lower levels of the antioxidant enzyme superoxide dismutase 2 compared to WT mice. Therefore, this study (i) reveals the onset of oxidative stress in brain cortices from OPA1+\/\u2212 mice challenged with a HFD, (ii) shows that diet is a modifying factor for DOA, and (iii) suggests that food control could be used to moderate the severity of the disease.<\/jats:p>","DOI":"10.3390\/antiox14070876","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T13:00:51Z","timestamp":1752757251000},"page":"876","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A High-Fat Diet Induces Oxidative Stress in OPA1+\/\u2212 Mouse Cortices: A Critical Double Challenge"],"prefix":"10.3390","volume":"14","author":[{"given":"Camille","family":"Champigny","sequence":"first","affiliation":[{"name":"Got-It Team, RESTORE\u2014University of Toulouse, CNRS ERL5311, EFS, INP-ENVT, Inserm U1031, B\u00e2timent INCERE, 4bis avenue Hubert Curien, 31100 Toulouse, France"},{"name":"Minding Team, Research Center on Animal Cognition (CRCA), Center of Integrative Biology (CBI)\u2014University of Toulouse, CNRS, 31067 Toulouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marl\u00e8ne","family":"Botella","sequence":"additional","affiliation":[{"name":"Minding Team, Research Center on Animal Cognition (CRCA), Center of Integrative Biology (CBI)\u2014University of Toulouse, CNRS, 31067 Toulouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6711-6951","authenticated-orcid":false,"given":"Djamaa","family":"Atamena","sequence":"additional","affiliation":[{"name":"Minding Team, Research Center on Animal Cognition (CRCA), Center of Integrative Biology (CBI)\u2014University of Toulouse, CNRS, 31067 Toulouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00e9bastien","family":"Bullich","sequence":"additional","affiliation":[{"name":"Remember Team, Research Center on Animal Cognition (CRCA), Center of Integrative Biology (CBI)\u2014University of Toulouse, CNRS, 31067 Toulouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corentin","family":"Coustham","sequence":"additional","affiliation":[{"name":"Got-It Team, RESTORE\u2014University of Toulouse, CNRS ERL5311, EFS, INP-ENVT, Inserm U1031, B\u00e2timent INCERE, 4bis avenue Hubert Curien, 31100 Toulouse, France"},{"name":"Minding Team, Research Center on Animal Cognition (CRCA), Center of Integrative Biology (CBI)\u2014University of Toulouse, CNRS, 31067 Toulouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6873-9966","authenticated-orcid":false,"given":"Bruno","family":"Guiard","sequence":"additional","affiliation":[{"name":"Remember Team, Research Center on Animal Cognition (CRCA), Center of Integrative Biology (CBI)\u2014University of Toulouse, CNRS, 31067 Toulouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0229-5554","authenticated-orcid":false,"given":"Pascale","family":"Belenguer","sequence":"additional","affiliation":[{"name":"Minding Team, Research Center on Animal Cognition (CRCA), Center of Integrative Biology (CBI)\u2014University of Toulouse, CNRS, 31067 Toulouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"No\u00e9lie","family":"Davezac","sequence":"additional","affiliation":[{"name":"Got-It Team, RESTORE\u2014University of Toulouse, CNRS ERL5311, EFS, INP-ENVT, Inserm U1031, B\u00e2timent INCERE, 4bis avenue Hubert Curien, 31100 Toulouse, France"},{"name":"Minding Team, Research Center on Animal Cognition (CRCA), Center of Integrative Biology (CBI)\u2014University of Toulouse, CNRS, 31067 Toulouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Cavaliere, G., Trinchese, G., Penna, E., Cimmino, F., Pirozzi, C., Lama, A., Annunziata, C., Catapano, A., Mattace Raso, G., and Meli, R. 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