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

Front Cell Neurosci. 2023 Nov 9:17:1294420. doi: 10.3389/fncel.2023.1294420. eCollection 2023.

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.

Keywords: Alzheimer’s disease; Parkinson’s disease; adipokines; cognitive impairment; inflammation; multiple sclerosis; neurodegenerative diseases; obesity.

Publication types

  • Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the grant Aviso n.° BI/8/FARM-ID/2022 to AN from Fundação para a Ciência e a Tecnologia (FCT). This work was funded by grants from FCT (EXPL/MED-NEU/1033/2021) to AB and FCT (UIDB/04138/2020 and UIDP/04138/2020) to iMed.ULisboa.