a Department of Biology , North Carolina Agricultural and Technical State University , Greensboro , NC 27411 , USA.
b Department of Nutrition , The University of North Carolina at Greensboro , Greensboro , NC 27412 , USA.
Nutr Neurosci. 2019 May;22(5):335-343. doi: 10.1080/1028415X.2017.1387720. Epub 2017 Oct 16.
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 F-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 F-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.
铁稳态的重要性在大脑中尤为明显，铁缺乏会导致认知障碍，而铁积累与神经退行性疾病有关。肥胖与全身铁缺乏有关，但肥胖对大脑铁及其相关后果（包括神经退行性过程）的影响仍未得到探索。这项初步研究检查了饮食诱导肥胖对大脑区域铁、α-突触核蛋白表达和选定大脑区域中 F2-异前列腺素（氧化应激标志物）浓度的影响。
本研究的目的是阐明由于肥胖相关的铁含量改变而导致的选定大脑区域（例如中脑、海马体）对可能发生的神经退行性过程的脆弱性。
21 天大的雄性 C57BL/6J 小鼠用高脂肪饮食（脂肪热量的 60%）或对照脂肪饮食（脂肪热量的 10%）喂养 20 周。收集脑样本并解剖为海马体、中脑、纹状体和丘脑区域。测量选定区域的铁含量、铁蛋白 H（FtH）和α-突触核蛋白蛋白和 mRNA 表达以及 F-异前列腺素。
结果表明，与对照小鼠相比，肥胖导致中脑和丘脑的铁水平出现显著差异，但海马体和纹状体没有差异。此外，中脑的神经退行性标志物（α-突触核蛋白 mRNA 表达和 F-异前列腺素）增加。
这些结果支持了先前的发现，即大脑铁代谢以区域特异性的方式对环境应激做出反应，并表明肥胖引起的大脑铁代谢改变可能与神经退行性变有关。
