Sex-Specific Differences Resulting from High Fat Diet Observed in Microglial Responses Across Varying Brain Regions
Abstract
Microglia are the resident immune cells in the nervous system, as they activate and release cytokines in response to immune challenges and maintain brain homeostasis. Consumption of a high fat diet and resulting metabolic disease (e.g. obesity and type 2 diabetes) alters microglial activity; however, studies have yet to explore sex differences in the effects of high fat diet/metabolic disease on microglia across several brain areas concurrently. This is vital given the heterogeneity of microglial distribution, morphology, and function across various pathological states. Male and female C57Bl/6J mice were fed either a low fat (LF; 10% fat) or high fat (HF; 60% fat) diet from 2-6 months of age. Body weight was measured weekly, and glucose tolerance testing was performed to assess diabetic status. Immunofluorescence was performed to quantify markers of microglia (Iba1) and phagocytosis (CD68) across subregions of the cortex, hippocampus, striatum, substantia nigra, amygdala, and hypothalamus, as well as white matter areas, such as the corpus callosum and fimbria. HF diet resulted in significantly increased weight gain and glucose intolerance (prediabetes) compared to LF diet to a similar degree in males and females. HF diet increased microglial activity in males but decreased it in females. Metabolic outcomes were associated in a sex-specific manner (positive correlation in males and negative correlation in females). These findings demonstrate the contrast of microglial responses in males and females following chronic consumption of a HF diet, which may contribute to the different rates of neurodegenerative and psychiatric diseases observed in men and women.
Faculty Sponsors
Dr. Lisa Robinson
Project Type
Event
Location
Alvin Sherman Library
Start Date
4-5-2023 12:00 PM
End Date
4-6-2023 4:00 PM
Sex-Specific Differences Resulting from High Fat Diet Observed in Microglial Responses Across Varying Brain Regions
Alvin Sherman Library
Microglia are the resident immune cells in the nervous system, as they activate and release cytokines in response to immune challenges and maintain brain homeostasis. Consumption of a high fat diet and resulting metabolic disease (e.g. obesity and type 2 diabetes) alters microglial activity; however, studies have yet to explore sex differences in the effects of high fat diet/metabolic disease on microglia across several brain areas concurrently. This is vital given the heterogeneity of microglial distribution, morphology, and function across various pathological states. Male and female C57Bl/6J mice were fed either a low fat (LF; 10% fat) or high fat (HF; 60% fat) diet from 2-6 months of age. Body weight was measured weekly, and glucose tolerance testing was performed to assess diabetic status. Immunofluorescence was performed to quantify markers of microglia (Iba1) and phagocytosis (CD68) across subregions of the cortex, hippocampus, striatum, substantia nigra, amygdala, and hypothalamus, as well as white matter areas, such as the corpus callosum and fimbria. HF diet resulted in significantly increased weight gain and glucose intolerance (prediabetes) compared to LF diet to a similar degree in males and females. HF diet increased microglial activity in males but decreased it in females. Metabolic outcomes were associated in a sex-specific manner (positive correlation in males and negative correlation in females). These findings demonstrate the contrast of microglial responses in males and females following chronic consumption of a HF diet, which may contribute to the different rates of neurodegenerative and psychiatric diseases observed in men and women.
