TY - JOUR
T1 - High-Fat Diet-Induced Obesity Increases Brain Mitochondrial Complex I and Lipoxidation-Derived Protein Damage
AU - Berdún, Rebeca
AU - Obis, Èlia
AU - Mota-Martorell, Natàlia
AU - Bassols, Anna
AU - Valent, Daniel
AU - Serrano, José C. E.
AU - Martín-Garí, Meritxell
AU - Rodríguez-Palmero, María
AU - Moreno-Muñoz, José Antonio
AU - Tibau, Joan
AU - Quintanilla, Raquel
AU - Pamplona, Reinald
AU - Portero-Otín, Manuel
AU - Jové, Mariona
N1 - Publisher Copyright:
© 2024 by the authors.
PY - 2024/1/26
Y1 - 2024/1/26
N2 - 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.
AB - 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.
KW - age-related neurodegenerative diseases
KW - lipoxidation
KW - mitochondrial complexes
KW - n3 PUFA
KW - obesity
KW - probiotics
UR - https://www.mendeley.com/catalogue/b3b294e4-bc83-3c8f-afe7-a86860efde2a/
UR - http://www.scopus.com/inward/record.url?scp=85187288343&partnerID=8YFLogxK
U2 - 10.3390/antiox13020161
DO - 10.3390/antiox13020161
M3 - Article
C2 - 38397759
SN - 2076-3921
VL - 13
JO - Antioxidants
JF - Antioxidants
IS - 2
M1 - 161
ER -