Sex and Genetic Factors Involved in Alterations of Behavior and Trace Element Neurobiology Due to Diet-Induced Obesity (P14-029-19)

Abstract

ObjectivesObesity has been linked to cognitive deficits, behavior issues, and neurodegenerative processes with trace element dysregulation as a potential trigger for their development. Sex and genetics are important factors to consider when evaluating the effects of diet-induced obesity (DIO) on neurophysiology and behavior changes. The objective of this study was to investigate sex and genetic differences on the disturbance of trace element brain biology and behavior due to DIO in male and female C57BL/6J (C57) and DBA/2J (DBA) mice. We hypothesize that alterations due to DIO will be more evident in males than females, and the DBA strain will show more resistance to DIO effects compared to the C57 strain. MethodsMale and female C57 (n = 36) and DBA (n = 36) mice at 21 days old were randomly assigned a control fat diet (CFD) with 10% kcal fat/g or mineral-matched high fat diet (HFD) with 60% kcal fat/g for 16 weeks. Behavior tests for anxiety, cognition, and memory included open field (OF), novel object recognition (NOR), and nestlet shredding (NS). Trace elements iron (Fe), copper (Cu), and manganese (Mn) were measured using graphite furnace atomic absorption spectroscopy in five brain regions. Statistical analysis was conducted using factorial ANOVA and repeated measures ANOVA. ResultsAfter 16 weeks, both strains fed the HFD were confirmed obese by body mass comparison (P < 0.001). A statistically significant interaction between diet and sex was observed for C57 mice in the OF evaluation of center time (P = 0.019), with obese females exhibiting more anxiety. Differences in NS due to DIO were found in male C57 mice only (P = 0.008). NOR performance was similar for all mice. There was a statistically significant diet by sex interaction for Fe in the striatum (P = 0.032) with opposite trends by sex. Diet by strain interactions were observed for Cu in the cortex and hippocampus, and for Mn in the thalamus. ConclusionsMale and female mice exhibit different behavior patterns and trace element distribution in the brain due to DIO, with more pronounced effects in the C57 strain compared to the DBA strain. Based on these findings, sex and genetics are important influences to consider when studying the consequences of obesity. Funding SourcesUNCG Health and Human Sciences Research Grant and Faculty First Award.