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

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

The Effects of Dietary Fat and Iron Interaction on Brain Regional Iron Contents and Stereotypical Behaviors in Male C57BL/6J Mice.

Adequate brain iron levels are essential for enzyme activities, myelination, and neurotransmitter synthesis in the brain. Although systemic iron deficiency has been found in genetically or dietary-induced obese subjects, the effects of obesity-associated iron dysregulation in brain regions have not been examined. The objective of this study was to examine the effect of dietary fat and iron interaction on brain regional iron contents and regional-associated behavior patterns in a mouse model. Thirty C57BL/6J male weanling mice were randomly assigned to six dietary treatment groups (n = 5) with varying fat (control/high) and iron (control/high/low) contents. The stereotypical behaviors were measured during the 24th week. Blood, liver, and brain tissues were collected at the end of the 24th week. Brains were dissected into the hippocampus, midbrain, striatum, and thalamus regions. Iron contents and ferritin heavy chain (FtH) protein and mRNA expressions in these regions were measured. Correlations between stereotypical behaviors and brain regional iron contents were analyzed at the 5% significance level. Results showed that high-fat diet altered the stereotypical behaviors such as inactivity and total distance traveled (P < 0.05). The high-fat diet altered brain iron contents and FtH protein and mRNA expressions in a regional-specific manner: (1) high-fat diet significantly decreased the brain iron content in the striatum (P < 0.05), but not other regions, and (2) thalamus has a more distinct change in FtH mRNA expression compared with other regions. Furthermore, high-fat diet resulted in a significant decreased total distance traveled and a significant correlation between iron content and sleeping in midbrain (P < 0.05). Dietary iron also decreased brain iron content and FtH protein expression in a regionally specific manner. The effect of interaction between dietary fat and iron was observed in brain iron content and behaviors. All these findings will lay foundations to further explore the links among obesity, behaviors, and brain iron alteration.