Abstract
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.
Highlights
Two-thirds of the population in the US are considered overweight or obese, and this number continues to rise
Mice fed with high fat diet had significantly higher energy intake than mice fed with the control fat diet at all iron levels (HF vs. CF, P < 0.05)
Mice fed with high fat diets, at both control and high iron levels, had a significant higher body weight compared with their control fat fed pairs (HF/CI vs. CF/CI, HF/HI vs. CF/HI, P < 0.05)
Summary
Two-thirds of the population in the US are considered overweight or obese, and this number continues to rise. One of the most recently studied obesity-associated disorders, systemic iron deficiency (ID), has sparked. An inverse relationship between body mass index (BMI) and plasma iron concentrations was observed in obese children [1]. Genetic obese adult mice (ob/ ob) showed lower iron concentrations in liver, muscle, femur, bone, and plasma than lean mice [6, 7]. Dietary-induced obese mice showed a significant decrease of hepatic non-heme iron contents after 16 weeks of high-fat treatment [8]. A decreased liver iron content and increased inflammation (hepcidin and IL-6) in adipose tissue was observed in a 24-week dietary-induced Swiss mice model [9]. All above studies focused on body iron stores or status affected by obesity. The brain regional iron content affected by high-fat diet has not yet been explored
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