Obesity and Neurodegeneration

Abstract

Obesity has become a major health problem in the last few decades, mainly due to change of society towards sedentary lifestyle, intake of high-calorie diets and reduction in physical activity. Obesity is characterized by excess storage of fat in muscles and adipose tissues. It brings along with it physiological changes to the body such as insulin resistance, hyperinsulinemia, dyslipidemia, adipokine secretion by adipose tissues. These physiological changes have a stark impact on proper brain functioning and may induce oxidative stress, ER stress and mitochondrial dysfunction. Obesity affects the glucose and energy metabolism of the brain cells and through the secretion of pro-inflammatory agents like TNF-α, IL-1, IL-6 induces neuroinflammation mainly in the hypothalmic region of the brain. The overall effect is impairment of neuronal function and its internal molecular machinery, resulting in aberrant protein depositions either intracellularly or extracellularly or both, thus leading to neurodegeneration. Obesity and neurodegenerative diseases (NDDs) are linked by alterations in molecular pathways such as P13K/Akt signaling pathway and IKKβ/NF-κB pathway, which may change expression profiles of genes or activate or deactivate molecular mediators and thereby drift away from normal cell functioning. Herein, we have discussed (i) Physiological alterations occurring during obesity and their potential link between neurodegenerative diseases. (ii) The signaling pathways affected during obesity and their impact on neurodegeneration and (iii) a list of gene involved in obesity mediated neurodegeneration.