High-Fat Diet-Induced Obesity Increases Brain Mitochondrial Complex I and Lipoxidation-Derived Protein Damage.
Rebeca BerdúnElia ObisNatàlia Mota-MartorellAnna BassolsDaniel ValentJosé C E SerranoMeritxell Martín-GaríMaría Rodríguez-PalmeroJosé Antonio Moreno-MuñozJoan TibauRaquel QuintanillaReinald PamplonaManuel Portero-OtinMariona JovéPublished in: Antioxidants (Basel, Switzerland) (2024)
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.
Keyphrases
- insulin resistance
- high fat diet
- fatty acid
- high fat diet induced
- oxidative stress
- adipose tissue
- metabolic syndrome
- resting state
- mass spectrometry
- functional connectivity
- gas chromatography
- skeletal muscle
- white matter
- type diabetes
- body weight
- weight loss
- cerebral ischemia
- protein protein
- amino acid
- weight gain
- risk factors
- binding protein
- multiple sclerosis
- subarachnoid hemorrhage
- tandem mass spectrometry
- healthcare
- liquid chromatography
- high performance liquid chromatography
- working memory
- health information
- gas chromatography mass spectrometry
- high resolution
- ms ms
- physical activity