The impact of obesity on brain iron levels and α-synuclein expression is regionally dependent

The importance of iron homeostasis is particularly apparent in the brain, where iron deficiency results in impaired cognition and iron accumulation is associated with neurodegenerative diseases. Obesity is linked to iron deficiency systemically, but the effects of obesity on brain iron and its associated consequences, including neurodegenerative processes remain unexplored. This preliminary study examined the effect of dietary-induced obesity on brain regional iron, α-synuclein expression, and F2-isoprostane (oxidative stress marker) concentrations in selected brain regions.

The objective of the study was to elucidate the vulnerability of selected brain regions (e.g. midbrain, hippocampus) to the possible process of neurodegeneration due to the altered iron content associated with obesity.

Twenty-one-day-old male C57BL/6J mice were fed with a high-fat diet (60% kcal from fat) or a control-fat diet (10% kcal from fat) for 20 weeks. Brain samples were collected and dissected into hippocampus, midbrain, striatum, and thalamus regions. Iron content, ferritin H (FtH) and α-synuclein protein and mRNA expressions, and F₂-isoprostane were measured in selected regions.

The results indicated that obesity caused significant differences in iron levels in the midbrain and thalamus, but not in the hippocampus or striatum, compared to control mice. Furthermore, markers of neurodegeneration (α-synuclein mRNA expression and F₂-isoprostanes) were increased in the midbrain.

These results support previous findings that brain iron metabolism responds to environmental stress in a regionally distinct manner and suggests that alterations in brain iron metabolism due to obesity may be relevant in neurodegeneration.