The complex relationship between obesity and neurodegenerative diseases: an updated review

Abstract

Obesity is a global epidemic, affecting roughly 30% of the world’s population and predicted to rise. This disease results from genetic, behavioral, societal, and environmental factors, leading to excessive fat accumulation, due to insufficient energy expenditure. The adipose tissue, once seen as a simple storage depot, is now recognized as a complex organ with various functions, including hormone regulation and modulation of metabolism, inflammation, and homeostasis. Obesity is associated with a low-grade inflammatory state and has been linked to neurodegenerative diseases like multiple sclerosis (MS), Alzheimer’s (AD), and Parkinson’s (PD). Mechanistically, reduced adipose expandability leads to hypertrophic adipocytes, triggering inflammation, insulin and leptin resistance, blood-brain barrier disruption, altered brain metabolism, neuronal inflammation, brain atrophy, and cognitive decline. Obesity impacts neurodegenerative disorders through shared underlying mechanisms, underscoring its potential as a modifiable risk factor for these diseases. Nevertheless, further research is needed to fully grasp the intricate connections between obesity and neurodegeneration. Collaborative efforts in this field hold promise for innovative strategies to address this complex relationship and develop effective prevention and treatment methods, which also includes specific diets and physical activities, ultimately improving quality of life and health.

Adiponectin Gene Polymorphisms: A Case–Control Study on Their Role in Late-Onset Alzheimer’s Disease Risk

“…Midlife adiposity and late-life weight loss are frequently linked to a higher risk of cognitive decline and AD in observational studies [ 9 , 10 ]. However, the exact nature of this relationship remains a source of controversy and may even involve reverse causation between a decline in body mass index (BMI) in later life and AD [ 11 , 12 , 13 , 14 , 15 , 16 , 17 ].…”

Insulin resistance as the molecular link between diabetes and Alzheimer's disease

“…The interplay between metabolic and neurodegenerative disorders has emerged as a focal point of scientific inquiry, highlighting the complex relationship between insulin resistance (IR) and Alzheimer's disease (AD)[ 1 - 3 ]. While Type 2 diabetes mellitus (T2DM) stands as a global concern predominantly characterized by IR, the scope of research extends beyond T2DM to elucidate IR's broader impact on neurological health[ 4 ].…”