94b81327e6fc4a9cfdc699a1d0ce4566 pmc_10886272.pdf 6f125944f5750d10574fbb5d2d1e962b3038cfc8 pmc_10886272.pdf 7ec2ab7271b8b704e0577f8424f950b623165d4233cfe3bc190b834f96d57e59 pmc_10886272.pdf Title: High-Fat Diet-Induced Obesity Increases Brain Mitochondrial Complex I and Lipoxidation-Derived Protein Damage Subject: Obesity is a risk factor for highly prevalent age-related neurodegenerative diseases, the pathogenesis of whichinvolves mitochondrial dysfunction and protein oxidative damage. Lipoxidation, driven by high levels of peroxidizable unsaturated fatty acids and low antioxidant protection of the brain, stands out as a significant risk factor. To gain information on the relationship between obesity and brain molecular damage, in a porcine model of obesity we evaluated (1) the level of mitochondrial respiratory chain complexes, as the main source of free radical generation, by Western blot; (2) the fatty acid profile by gas chromatography; and (3) the oxidative modification of proteins by mass spectrometry. The results demonstrate a selectively higher amount of the lipoxidation-derived biomarker malondialdehyde-lysine (MDAL) (34% increase) in the frontal cortex, and positive correlations between MDAL and LDL levels and body weight. No changes were observed in brain fatty acid profile by the high-fat diet, and the increased lipid peroxidative modification was associated with increased levels of mitochondrial complex I (NDUFS3 and NDUFA9 subunits) and complex II (flavoprotein). Interestingly, introducing n3 fatty acids and a probiotic in the high-fat diet prevented the observed changes, suggesting that dietary components can modulate protein oxidative modification at the cerebral level and opening new possibilities in neurodegenerative diseases’ prevention. Keywords: obesity; lipoxidation; mitochondrial complexes; n3 PUFA; probiotics; age-related neurodegenerative diseases Author: Rebeca Berdún, Èlia Obis, Natàlia Mota-Martorell, Anna Bassols, Daniel Valent, José C. E. Serrano, Meritxell Martín-Garí, María Rodríguez-Palmero, José Antonio Moreno-Muñoz, Joan Tibau, Raquel Quintanilla, Reinald Pamplona, Manuel Portero-Otín and Mariona Jové Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Mon Jan 29 08:30:51 2024 CET ModDate: Mon Jan 29 08:35:26 2024 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 15 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1458832 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- NJQAJI+VnURWPalladioL-Bold Type 1 Custom yes yes yes 10 0 NWDPTK+URWPalladioL-Bold Type 1 Custom yes yes yes 16 0 GMZBCM+URWPalladioL-Roma Type 1 Custom yes yes yes 22 0 FYVPXS+URWPalladioL-Ital Type 1 Custom yes yes yes 27 0 NRLQOR+VnURWPalladioL Type 1 Custom yes yes yes 32 0 KUDXZB+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 48 0 QMDDXF+CMSY10 Type 1 Builtin yes yes yes 68 0 CYGDXG+EURM10 Type 1 Builtin yes yes yes 76 0 RIQEPZ+URWPalladioL-BoldItal Type 1 Custom yes yes yes 84 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 97 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 101 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 105 0 BCDHEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 109 0 ROWTUD+PazoMath Type 1 Builtin yes yes yes 124 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 137 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 141 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 145 0 BCDHEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 149 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 166 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 170 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 174 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-04-18 02:40:37 CEST RepresentationInformation: pmc_10886272.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-04-09 02:35:38 CEST Size: 1458832 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 392 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Design and Ethics Destination: subsection.2.1 Item: Title: Protein Non-Enzymatic Modification Markers Destination: subsection.2.2 Item: Title: Mitochondrial Electron Transport Chain Complexes Destination: subsection.2.3 Item: Title: FA Profile of the PFC Lipidome Destination: subsection.2.4 Item: Title: Statistics Destination: subsection.2.5 Item: Title: Results Destination: section.3 Children: Item: Title: Biochemical and Phenotipic Differences between Pigs Fed Different Diets Destination: subsection.3.1 Item: Title: A Western-Type Diet Increases Protein Lipoxidative Modifications on the Brain Cortex Destination: subsection.3.2 Item: Title: The Brain Cortex Protein Lipoxidative Modifications Induced by the Western Diet Are Not Due to Changes in FA Composition Destination: subsection.3.3 Item: Title: Western-Type Diet Is Associated with Changes in the Content of Mitochondrial Respiratory Complexes Destination: subsection.3.4 Item: Title: Dietary Supplementation with Vegetal Protein with Bifidobacterium Breve CECT8242 Alone or in Combination with n3 Fatty Acids Can Partially Revert the Effects of a Western-Type Diet in the Brain Cortex Protein Lipoxidative Damage Destination: subsection.3.5 Item: Title: Lipoxidation-Derived Protein Damage in the Brain Cortex Correlates with Peripheral Lipids Destination: subsection.3.6 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: appendix.A. Info: Title: High-Fat Diet-Induced Obesity Increases Brain Mitochondrial Complex I and Lipoxidation-Derived Protein Damage Author: Rebeca Berdún, Èlia Obis, Natàlia Mota-Martorell, Anna Bassols, Daniel Valent, José C. E. Serrano, Meritxell Martín-Garí, María Rodríguez-Palmero, José Antonio Moreno-Muñoz, Joan Tibau, Raquel Quintanilla, Reinald Pamplona, Manuel Portero-Otín and Mariona Jové Subject: Obesity is a risk factor for highly prevalent age-related neurodegenerative diseases, the pathogenesis of whichinvolves mitochondrial dysfunction and protein oxidative damage. Lipoxidation, driven by high levels of peroxidizable unsaturated fatty acids and low antioxidant protection of the brain, stands out as a significant risk factor. To gain information on the relationship between obesity and brain molecular damage, in a porcine model of obesity we evaluated (1) the level of mitochondrial respiratory chain complexes, as the main source of free radical generation, by Western blot; (2) the fatty acid profile by gas chromatography; and (3) the oxidative modification of proteins by mass spectrometry. The results demonstrate a selectively higher amount of the lipoxidation-derived biomarker malondialdehyde-lysine (MDAL) (34% increase) in the frontal cortex, and positive correlations between MDAL and LDL levels and body weight. No changes were observed in brain fatty acid profile by the high-fat diet, and the increased lipid peroxidative modification was associated with increased levels of mitochondrial complex I (NDUFS3 and NDUFA9 subunits) and complex II (flavoprotein). Interestingly, introducing n3 fatty acids and a probiotic in the high-fat diet prevented the observed changes, suggesting that dietary components can modulate protein oxidative modification at the cerebral level and opening new possibilities in neurodegenerative diseases’ prevention. 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