How do extreme changes in body weight affect the brain?
Disorders of energy balance (e.g. obesity, cachexia, anorexia) involve a complex interaction of genetics, diet, activity and metabolism. However, changes in inflammatory state are now known to be present during situations of altered energy homeostasis. For example, obesity has been proposed to be an ‘inflammatory disease’, as low-grade inflammation is detected in obese subjects, measured by increases in inflammatory markers (e.g. C-reactive protein, tumor necrosis factor-α, interleukin-6, leptin) in the serum. These inflammatory changes are now thought to contribute to some of the diseases linked with obesity. We are interested in understanding how these inflammatory processes affect the central nervous system (CNS).
Obesity is associated with an increased risk of several diseases, such as diabetes and some cardiovascular conditions. Recent data also suggest that obesity constitutes a risk factor for damage to the CNS, although the mechanism involved in these actions is unknown. Inflammation plays a major role in several disorders that affect the CNS, such as the neuronal injury observed during cerebral ischaemia (stroke) and Alzheimer’s disease. Thus, the overall aim of our work is to understand if changes in inflammation observed during situations of altered energy balance (e.g. positive energy balance in obesity) lead to altered CNS responses to injury, by using appropriate experimental in vivo models combined with in vitro approaches. This work will have relevance to acute forms of neuronal injury, such as stroke, but also to neuronal damage in chronic forms of neurodegeneration (e.g. Alzheimer’s disease).