Antioxidants (Jan 2024)

High-Fat Diet-Induced Obesity Increases Brain Mitochondrial Complex I and Lipoxidation-Derived Protein Damage

  • 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,
  • Mariona Jové

DOI
https://doi.org/10.3390/antiox13020161
Journal volume & issue
Vol. 13, no. 2
p. 161

Abstract

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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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