LAUSR

Objectives Iron (Fe), Copper (Cu), and Manganese (Mn) are essential trace elements that are critical for health and must be maintained in an optimal physiological range. When there is a disturbance of this regulation, such as obesity, pathologies ranging from anemia to neurotoxicity can occur. The objective of this current study is to examine strain and sex differences in the distribution of systemic trace elements due to diet-induced obesity (DIO). We hypothesize that high fat DIO causes significant systemic alterations of Fe, Cu, Mn distributions compared to low fat diet with sex and strain as contributing factors. Methods Beginning at 21 days of age, male and female C57BL/6 J (n = 36) and DBA/2 J (n = 36) mice were fed either a high-fat diet (60% Kcal from fat) or a control diet (10% Kcal from fat) for 16 weeks. Food intake and body mass were measured weekly. At the end of the 16 weeks, blood, liver, and spleen tissues were collected. Fe, Cu, and Mn concentrations were measured using graphite furnace atomic absorption spectroscopy. Results While DIO did not cause any strain or sex differences in hematocrit, differences were detected in all three metals, Mn, Cu, and Fe concentrations in the liver and spleen. Specifically, there was a statistically significant sex by diet interaction on liver Mn concentrations (P = 0.008) and strain by sex interaction on spleen Mn concentrations (P = 0.002). There was a sex by diet and strain by sex interaction on liver Cu concentrations (P = 0.01 and P = 0.006, respectively). A three-way strain, sex, and diet interaction (P = 0.003) was observed for Cu in spleen. There was a strain by sex and strain by diet interaction on liver Fe concentrations (P = 0.031 and P = 0.002, respectively). There was a statistically significant strain, sex, and diet interaction on spleen Fe concentrations (P = 0.0002). The most prominent interactive effects of sex, strain and DIO was observed with liver and spleen Fe concentrations compared to Cu or Mn. For example, male DBA and female C57 mice had greatly reduced Fe in liver and spleen but their opposite sex counterparts were largely unaffected by the impact of DIO. Conclusions Our results expand our previous data by showing strain and sex differences not only in Fe, but Cu and Mn systemic concentrations. For females, the impact of DIO on Fe was more significant in the C57 strain whereas in males the effect of DIO was more significant in the DBA strain. Funding Sources UNCG Health and Human Sciences Research Grant & UNCG Faculty First Award.