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

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.
Original languageEnglish
Article number161
Number of pages15
JournalAntioxidants
Volume13
Issue number2
DOIs
Publication statusPublished - 26 Jan 2024

Keywords

  • age-related neurodegenerative diseases
  • lipoxidation
  • mitochondrial complexes
  • n3 PUFA
  • obesity
  • probiotics

Fingerprint

Dive into the research topics of 'High-Fat Diet-Induced Obesity Increases Brain Mitochondrial Complex I and Lipoxidation-Derived Protein Damage'. Together they form a unique fingerprint.

Cite this