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How Insulin resistance in the brain affects the metabolic behaviour and favours neurodegeneration.
Diabetes and obesity are epidemic diseases that are rising among the world population. Eight out of 10 men and almost 7 in 10 women will be overweight or obese by 2020 1. Most of these overweight/obese individuals are more prone to develop insulin resistance and diabetes. Overnutrition is the predominant pathogenic inducer of insulin resistance, which is mainly caused by increased circulating levels of glucose, free fatty acid (FFA) and amino acids 2,3. Increase of these circulating factors causes intracellular stresses such as mitochondrial oxidative stress and endoplasmic reticulum (ER) stress, which occur both in peripheral tissues 4 and in the Central Nervous System (CNS) 5. The CNS collects peripheral inputs to regulate the metabolic status of an individual and signals back to the periphery in order to keep a metabolic homeostasis. Any alteration of these processes can lead to a metabolic disease and vice versa. Since overnutrition affects the CNS regulatory functions, restoring the brain’s ability to modulate metabolic functions could be very important to overcome a pathological condition.
Bianca Patel (Primary supervisor) 50% FTE