Inhibition of microglia inflammation by AMPK for obesity treatment

Research Opportunity
PhD
Department
Medicine and Radiology
Location
St Vincent's Institute of Medical Research
Primary Supervisor Email Number Webpage
Dr Sandra Galic sgalic@unimelb.edu.au
Co-supervisor Email Number Webpage
Prof Bruce Kemp bkemp@svi.edu.au

Summary This project will investigate whether AMPK activation in microglia can suppress hypothalamic inflammation and damage of appetite-regulating neurons resulting in reduced body weight gain with high-fat feeding. The study will involve the isolation and culture of primary microglia and handling of knockout and transgenic mice to investigate hormone signalling pathways, gene expression, whole-body energy homeostasis and hepatic glucose production.

Project Details

Consumption of high-calorie diets is associated with the onset of inflammation in the hypothalamus, the main brain area involved in the regulation of appetite, energy expenditure and glucose homeostasis. This overnutrition-induced inflammation is mediated by microglia, which are macrophage-like cells that normally protect the brain from pathogens and help with clearance of cell debris. However, when chronically activated in response to dietary fatty acids, microglia generate an inflammatory environment within the hypothalamus that is toxic for neighbouring neurons and damages neuronal circuits that normally control energy homeostasis and hepatic glucose production. We have previously shown that the AMP-activated protein kinase (AMPK) has anti-inflammatory effects in bone marrow derived macrophages and inhibits adipose tissue inflammation associated with a high-fat diet. This project will investigate whether AMPK activation in microglia can suppress hypothalamic inflammation and damage of appetite-regulating neurons resulting in reduced body weight gain with high-fat feeding. The study will involve the isolation and culture of primary microglia and handling of knockout and transgenic mice to investigate hormone signalling pathways, gene expression, whole-body energy homeostasis and hepatic glucose production. Commonly used techniques will include brain immunohistochemistry, confocal microscopy, immunoblotting, Real-time PCR, ELISA, flow cytometry, calorimetry and body composition analyses by NMR.


School Research Themes

Cardiometabolic



Research Opportunities

PhD
Students who are interested in joining this project will need to consider their elegibility as well as other requirements before contacting the supervisor of this research

Graduate Research application

Honours application

Key Contact

For further information about this research, please contact a supervisor.

Department

Medicine and Radiology

Research Node

St Vincent's Institute of Medical Research

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